Proteopedia - User contributions [en]

https://proteopedia.org/api.php?action=feedcontributions&feedformat=atom&user=Joseph+Hardie Proteopedia - User contributions [en] 2026-09-20T15:49:20Z User contributions MediaWiki 1.43.8 https://proteopedia.org/index.php?title=CBI_Molecules&diff=2075580 CBI Molecules 2014-12-03T15:06:03Z

<p>Joseph Hardie: </p> <hr /> <div>These are molecules under study by members of the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program].<br /> Many of the molecules we study are featured at the [http://www.molecularplayground.org/ Molecular Playground] (see also [[Molecular Playground|Molecular Playground in Proteopedia]]). Follow the links below to read nontechnical descriptions, in Proteopedia, of these molecules.<br /> <br /> UMass CBI Members, add your molecules to the list (which is alphabetical by CBI research mentor); follow the instructions below the list.<br /> <br /> Fall 2014: CBI Molecules are due 12/3/14 and should be added at the TOP of the list from your lab. Label it as "in progress" until you are finished, and then as "New 2014" or "Revised 2014". For those editing an existing CBI Molecule, start by making a copy of that entry (leaving the original intact) so that it retains the full author list of all authors that contributed (or include credits and a link to the original page and authors if it does not).<br /> Follow the instructions at the bottom of this page.<br /> <br /> <br /> ==Molecules==<br /> '''** Designates CBI Molecules Featured on [http://www.umass.edu/cbi/ CBI website]'''<br /> <br /> [http://chamberslab.com/wp/ Chambers Lab]<br /> <br /> : '''[[Molecular Playground/Glutamate Receptor]]''', Amanda Hussey, Steve McCarron, Rosie Combs-Bachmann, Mariel Feliciano<br /> <br /> <br /> [http://www.chem.umass.edu/~chenlab/index.HTML Chen Lab]<br /> <br /> : '''[[Molecular Playground/ClyA]]''', Bib Yang<br /> : '''[[Molecular Playground/OmpG]]''', Christina Chisholm<br /> <br /> <br /> [http://openwetware.org/wiki/Chien Chien Lab]<br /> <br /> : '''[[Molecular Playground/Homo-dimeric RcdA]]''', Kamal K. Joshi <br /> : **'''[[Molecular Playground/Hexameric ClpX]]''', Joanne Lau '''Best CBI Molecule 2011'''<br /> : '''[[Molecular Playground/DNA replication initiator DnaA]]''', Jing Liu<br /> <br /> <br /> Farkas Lab<br /> : '''[[Molecular Playground/CLOCK:BMAL1 heterodimer complex]]''', Hui-Hsien Lin, Joseph Hardie, Michael Mingroni '''New 2014''' <br /> <br /> Forbes Lab<br /> <br /> : '''[[Molecular Playground/CheR]]''', Miaomin Zhang<br /> : '''[[Molecular Playground/RBP]]''', Jan Panteli<br /> : '''[[Molecular Playground/TRAIL]]''', Charley Swofford<br /> <br /> <br /> [http://www.biochem.umass.edu/garman/index.html Garman Lab]<br /> <br /> : '''[[Molecular Playground/Human Protective Protein Cathepsin A]]''', Yadilette Rivera-Colon<br /> : '''[[Molecular Playground/Human PPCA]]''', Nilima Kolli<br /> <br /> <br /> [http://people.chem.umass.edu/gieraschlab/ Gierasch Lab]<br /> <br /> : '''[[Molecular_Playground/DnaK]]''', Joseph Tilitsky, New 2014<br /> : '''[[CRABP I ( Cellular Retinoic Acid Binding Protein )|Molecular Playground/CRABP I]]''', Kristine Faye Pobre, Mylene Ferrolino,Mangai Periasamy '''Best Overall CBI Molecule 2010'''<br /> : '''[[Molecular Playground/CRABP I (Cellular Retinoic Acid Binding Protein)]]''', Gustavo Elberto Epalza Sanchez<br /> : **'''[[Molecular_Playground/DHFR]]''', Karan Hingorani '''Best CBI Molecule 2012'''<br /> <br /> <br /> [http://people.chem.umass.edu/jhardy/ Hardy Lab]<br /> <br /> : '''[[Molecular Playground/Executioner Caspase-7]]''', Derek MacPherson, Maureen E. Hill<br /> : '''[[Molecular Playground/Caspase-3 Regulatory Mechanisms]]''', Scott Eron, Bay Serrano, Yunlong Zhao<br /> : '''[[Molecular Playground/Caspase-6 and neurodegeneration]]''', Kevin Buadlart Dagbay<br /> : '''[[Molecular Playground/Caspase-7 Dynamics]]'''<br /> : '''[[Molecular Playground/Caspase-9 Regulation]]''', Kristen Huber<br /> : '''[[Molecular Playground/Caspase-6 (new)]]''', Elih Velazquez<br /> : '''[[Molecular Playground/Influenza A M2 transmembrane domain]]''', Samantha Nicholls<br /> : '''[[Molecular Playground/Dengue Virus Protease]]''', Muslum Yildiz<br /> <br /> <br /> Hebert Lab<br /> <br /> : '''[[Molecular_Playground/Hsp70-Hsp90]]''', Jill Graham<br /> : '''[[Molecular_Playground/ERDj5]]''', Lydia Lamriben<br /> : '''[[Molecular Playground/Saposin C]]''', Abla Tannous<br /> : '''[[Molecular_Playground/ERMan1]]''', Johan Sunryd<br /> <br /> <br /> [http://people.biochem.umass.edu/aheuck/aph.html Heuck Lab]<br /> <br /> : '''[[Molecular_Playground/Pcr H]]''', Fabian Romano, Carolina Morell-Pérez<br /> <br /> <br /> [http://people.chem.umass.edu/mholden/ Holden Lab]<br /> <br /> : '''[[Molecular Playground/Protective Antigen]]''', Jing Huang<br /> <br /> <br /> [http://www.chem.umass.edu/people/kaltashovlab/ Kaltashov Lab]<br /> <br /> : '''[http://proteopedia.org/wiki/index.php/Chengfeng_Ren Molecular Playground/Inteferon]'''[Revised], Chengfeng Ren<br /> : ''' [[Molecular Playground/Transferrin]]''', Khaja Muneeruddin, Jake Pawlowski<br /> : '''[[Molecular Playground/Velaglucerase]]''', Adriana Kita<br /> : '''[[Molecular Playground/Antithrombin-Heparin]]''', Yunlong Zhao<br /> <br /> <br /> Knapp lab<br /> <br /> : '''[[Molecular Playground/FIH]]''', Vanessa Chaplin, Cornelius Taabazuing, Breanne Holmes, John Hangasky<br /> : '''[[Molecular Playground/Prolyl Hydroxylase Domain (PHD) Enzyme]]''', Cristina Martin, Serap Pektas '''Best CBI Molecule Proteopedia Page 2010'''<br /> <br /> <br /> <br /> [http://people.chem.umass.edu/mmaroney/ Maroney Lab]<br /> <br /> : '''[[Molecular Playground/UreE]]''', Priyanka Basak, '''New 2014'''<br /> : '''[[Molecular Playground/Nickel Superoxide Dismutase]]''', Carolyn Carr<br /> : '''[[Molecular Playground/CsoR and RcnR]]''', Heidi Hu, Carolyn Carr, Hsin-Ting (Tiffany )Huang, '''Revised 2014'''<br /> : '''[[Molecular Playground/HypA]]''', Heidi Hu<br /> <br /> <br /> [http://www.chem.umass.edu/~cmartin/ Martin Lab]<br /> <br /> : **'''[[Molecular Playground/T7 RNAP Conformations]]''', Luis E. Ramirez-Tapia '''Best CBI Molecule 2011'''<br /> : '''[[Molecular Playground/T7 RNA Polymerase (7 mer int)]]''', Ankit Vahia<br /> : '''[[Molecular Playground/Human mtRNA pol]]''', Ketan Mathavan <br /> <br /> <br /> [http://www.peytonlab.org/ Peyton Lab]<br /> : '''[[Molecular Playground/IntegrinBeta1]]''', Lauren Jansen, Lauren Barney, Elizabeth Brooks, Alyssa Schwartz ***'''NEW FALL 2014''''***<br /> : '''[[Molecular Playground/MMP14]]''', Lauren Jansen<br /> : '''[[Molecular Playground/C-Raf]]''', Thuy Nguyen<br /> : '''[[Molecular Playground/FAK]]''', Dannielle Ryman<br /> <br /> [http://roberts.openwetware.org/ Roberts Lab]<br /> <br /> : '''[[Molecular Playground/Taxol]]''', Rohan Patil, Sarah Wilson<br /> : '''[[Molecular Playground/Insulin]]''', Whitney Stoppel<br /> <br /> <br /> [http://www.umass.edu/rotellogroup/ Rotello Lab]<br /> <br /> : '''[[Reverse transcriptase|Molecular Playground/Reverse Transcriptase]]''', Daniel Moyano-Marino<br /> : '''[[Molecular Playground/Pancreatic Lipase]]''', Rui Tang<br /> : '''[[Molecular playground/Chymotrypsin]]''', Brad<br /> : '''[[Molecular Playground/Targeting Peptide]]''', David Solfiell<br /> <br /> <br /> [http://http://www.umass.edu/schiffman/ Schiffman Lab]<br /> : '''[[Molecular Playground/Streptavidin]]''', Katrina Rieger<br /> <br /> <br /> [http://www.biochem.umass.edu/faculty/danny-j-schnell Schnell Lab]<br /> : '''[[Molecular Playground/Tic40]]''', Mine Canakci<br /> <br /> <br /> Tew Lab<br /> <br /> : '''[[Molecular Playground/HIV Tat]]''', Brittany deRonde<br /> <br /> <br /> Thayumanavan Lab<br /> : '''[[Interleukin-1 beta]]''', Huan He<br /> : '''[[Molecular Playground/Lysozyme ]]''', Daniella Gonzalez<br /> : '''[[Molecular Playground/Beta-galactosidase]]''', Judy Ventura<br /> : '''[[User:Krishna Reddy Ragupathi|Molecular Playground/Carbonic Anhydrase]]''', Krishna Reddy Raghupathi<br /> : '''[[User:Rami Rajasekhar Reddy|Molecular Playground/Avidin]]''', Rami Rajasekar Reddy<br /> : '''[[Molecular Playground/Biotin binding avidin]]''', Diego Amado <br /> : '''[[User:Jiaming Zhuang|Molecular Playground/MMP12]]''', Jiaming Zhuang<br /> : ''' [[User:Jing Guo|Molecular Playground/Gluconase]]''', Jing Guo<br /> : '''[[Molecular Playground/Glutathione Reductase]]''', Reuben Chacko<br /> <br /> <br /> Thayumanavan & Vachet Labs<br /> <br /> : '''[[Molecular Playground/Trypsin]]''', Gladys Murage<br /> <br /> <br /> [http://people.chem.umass.edu/thompson/index.html Thompson Lab]<br /> <br /> : '''[[Molecular Playground/Bacterial Chemotaxis Complex]]''', Elizabeth R. Haglin, Maryam Kashefi<br /> : '''[[Molecular Playground/CheA]]''', Elizabeth R. Haglin<br /> : '''[[Molecular Playground/Bacterial Chemotaxis Receptors]]''', Lynmarie K. Thompson, Shiela M. Jones<br /> : '''[[Molecular Playground/Cytoplasmic domain of chemoreceptor of Thermotoga maritima]]''', Xuni Li<br /> <br /> <br /> [http://www.chem.umass.edu/~vachet/index.html Vachet Lab]<br /> <br /> : ''[[Molecular Playground/Human Serum Albumin]]''', Mahalia Serrano<br /> : '''[[Molecular playground/beta 2 microglobulin]]''', Nick Borotto '''Best CBI Molecule Jmol scenes 2010'''<br /> : '''[[Molecular Playground/Myoglobin]]''', Yuping Zhou <br /> :'''[[Molecular Playground/ Copper-Zinc Superoxide Dismutase]]''', Shaynah Browne<br /> : '''[[Molecular Playground/Ubiquitin salt bridge discussion]]''', Zhe Zhang<br /> <br /> <br /> Other Molecules of interest<br /> <br /> : '''[[Molecular Playground/PcrA Helicase]]''', Luis E Ramirez-Tapia, [http://www.chem.umass.edu/~cmartin/ Martin Lab]<br /> <br /> <br /> Other Laboratories<br /> <br /> :'''[[Molecular Playground/4'-PHOSPHOPANTETHEINYL TRANSFERASE (Sfp)]]''', Jon Amoroso, Gitanjeli Prasad, Lawrence Sheringham Borketey, Schnarr lab<br /> : '''[[6-deoxyerythronolide_B_synthase_(DEBS)|Molecular Playground/6-Deoxyerythronolide B Synthase]]''', Tsung-Yi Lin, Jon Amoroso, Lawrence Sheringham Borketey, Schnarr lab<br /> : '''[[Molecular Playground/ACP apo]]''', Gitanjeli Prasad, Schnarr lab<br /> <br /> : '''[[Molecular Playground/cytoplasmic domain of a serine chemotaxis receptor]]''', Meili Yang, Weis lab<br /> <br /> : '''[[Molecular Playground/Alginate-Fall2011]]''', Joe White, David Griffi, Bhatia Lab<br /> : '''[[Molecular Playground/Poly(ethylene glycol)]]''', Erika M. Saffer, Bhatia Lab<br /> <br /> : '''[[Molecular Playground/YKL-40]]''', Ralph A. Francescone III, [http://www.bio.umass.edu/mcb/faculty/Shao.html Shao Lab]<br /> <br /> : '''[[Molecular Playground/BLG|Molecular Playground/β-lactoglobulin]]''', Daniel Seeman, Dubin Lab<br /> <br /> : '''[[Molecular Playground/ADAM13]]''', Genevieve Abbruzzese, Alfandari Lab<br /> <br /> ==Instructions==<br /> <br /> '''The goal is for students to work collaboratively to create one excellent CBI Molecule for each CBI research group, to be featured on the CBI website.'''<br /> <br /> Fall 2014: Complete steps 1-3 before the CBI Molecule Workshop on 11/19; bring your computer to the CBI Molecule Workshop in ISB 321. You will be able to start work on your CBI Molecule at the workshop. You should plan to stay and finish your molecule after the workshop (or as soon as possible) while the instructions and ideas are fresh in your mind.<br /> <br /> A successful CBI Molecule is an interesting, nontechnical description of a molecule related to your group's research. It should tell an interesting story with few words and many green scenes. Green scenes should be clear and attractive illustrations that tell your story. It's great if you can end with a brief statement about how it relates to your group's research goals.<br /> <br /> 1. If you don't already have one, request a Proteopedia account and log in. <br /> <br /> 2. Read through the rest of the instructions, do the tutorials below, and look at any existing CBI Molecules from your research group. Talk with other CBI students in your research group and decide how you will collaborate to make an improved CBI Molecule related to your group's research. Develop ideas for the scenes that each of you will make.<br /> <br /> 3. Get started working in Proteopedia. Make yourself a sandbox page: Enter "User:Your Name/Sandbox 1" (omit quotes) in the search box, then follow instructions to edit this page. Practice entering text, inserting a structure window with scrolling text (green 4-square button on the right), and creating a green scene. Explore the HELP links below to learn how to make a green scene. You can look at other Proteopedia pages in edit mode to see how different effects (like colored text) are achieved (but this won't show you how the scene effects are made). <br /> <br /> '''Complete the above steps before the CBI Molecule Workshop.'''<br /> <br /> 4. When editing an existing CBI Molecule, leave the original intact and make a copy that you will edit so that it retains the full author list of all authors that contributed. You are encouraged to collaborate on the CBI Molecules, but everyone will need to log in as themself and create a green scene to get credit for their work and to appear as authors on the final list. If you are the sole student from your group enrolled in Chalk Talk and have not previously made a CBI Molecule, try to convince another group member who has previously made a CBI Molecule (see list above) to join us for the workshop so that you can work together.<br /> <br /> 5. Your final pages should be called "Molecular Playground/your molecule" and should have links on this CBI Molecule page -- put the new ones first on the list from your research group. Label them "in progress" until you are finished, and then "new 2014" or "revised 2014". Minimize text; tell your story with green scenes!<br /> <br /> 6. When your CBI Molecule is complete, send Lynmarie an email to nominate a cool scene/clever caption you would like to feature at the Molecular Playground (include a link to your CBI Molecule, name of the green scene, and caption).<br /> <br /> ==Links to HELP pages==<br /> Overview at [[Help:Contents ]]<br /> <br /> See also [[Help:Getting_Started_in_Proteopedia]] <br /> <br /> Videos showing how to use Proteopedia:<br /> [[Proteopedia:Video_Guide]]<br /> (Sometimes slow -- if you pause the video and wait awhile it will download and then you can play it without interruptions)<br /> <br /> [[Proteopedia:DIY:Scenes|Proteopedia Scenes: Do It Yourself]]<br /> gives succinct step by step instructions on how to create a molecular scene.<br /> <br /> A powerpoint-like set of slides that walks a user through the process of creating a new page and a new molecular scene/green link.<br /> [http://www.proteopedia.org/wiki/images/1/1b/2009_07_13_Proteopedia_Workshop.pdf Proteopedia Workshop Slides]<br /> <br /> [[Proteopedia:Guidelines for Ethical Writing]].<br /> Please pay attention to the section about images. There are links to examples of images re-used with explicit permission.<br /> <br /> For other help resources, click on [[Help:Contents|Help]] in the ''navigation'' box at the upper left of every page in Proteopedia.</div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2071909 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-12-03T00:57:36Z

<p>Joseph Hardie: </p> <hr /> <div>==CLOCK:BMAL1 heterodimer complex==<br /> <br /> <br /> <StructureSection load='4F3L' size='340' side='right' caption='mouse CLOCK:BMAL1 heterodimer complex' scene='60/609802/Clock_bmal1/1'><br /> The <scene name='60/609802/Clock_bmal1/1'>CLOCK:BMAL1 heterodimer complex</scene> is a vital regulatory component of the circadian rhythm protein regulation system. CLOCK (''Circadian Locomotor Output Cycles Kaput'') and BMAL1 (''Brain and muscle Arnt-like protein-1'') are <scene name='60/609802/Bhlh_ex/1'>the basic helix-loop-helix</scene> PER-ARNT-SIM (bHLH-PAS) proteins. (The structure highlighted in yellow is a portion of bHLH structure in CLOCK) The CLOCK:BMAL1 heterodimer is the main transcriptional activator in the mammalian circadian mechanism.<ref>DOI: 10.1126/science.280.5369.1564</ref> The binding between CLOCK and BMAL1 involves the N-terminal bHLH, PAS-A and PAS-B domains of both proteins. Each domain (bHLH, PAS-A, PAS-B) binds to its corresponding equivalent in the other protein. Though both proteins contain the same types of domains with similar primary amino acid sequences in each, the overall heterodimer is surprisingly asymmetrical due to differences in the spatial orientation of the domains in each protein. Since this heterodimer complex involves the binding of all of the major domains in both participating proteins, the overall binding affinity is very high.<br /> <br /> == Role in Circadian Rhythm ==<br /> <br /> Circadian rhythms are operated by an endogenous core clock system that drives daily rhythms in behavior, physiology, and metabolism. In mammalian systems, the suprachiasmatic nucleus (SCN), which is located in the hypothalamus, is the locus of a master circadian clock. The SCN controls the expression of of proteins in a time dependent manner through a genetic feedback loop initiated by light passing through the eye.<ref>doi: 10.1111/ejn.12593</ref> The core molecular clockwork is composed of a transcriptional/post-translational feedback loop: CLOCK:BMAL1 (transcriptional activators) and PER:CRY (transcriptional repressors). In daytime, CLOCK and BMAL1 will form a heterodimer complex to bind the E-box promoter region of other circadian rhythm proteins, causing the transcription of Per (''Period'') and Cry (''Cryptochrome''). During the day, Per and Cry will dimerize and translocate into the nucleus, where they interact with CLOCK:BMAL1 to inhibit their own transcription, forming a negative feedback loop.<ref>DOI: 10.1126/science.1222804</ref> At night time, Per:Cry complex is degraded by a specific E3 ligase complex and the repression is relieved. After the repression level of Per:Cry is decreased, CLOCK:BMAL1 will be re-activated and start transcription again, forming the positive feedback loop. The entire negative/positive feedback loop take around 24 hours to complete, thus forming the core mechanism of the circadian clock in mammals.<ref>doi:10.1016/B978-0-12-387690-4.00006-4</ref> <br /> <br /> ==The Overall structure of CLOCK:BMAL1 complex==<br /> <br /> The <scene name='60/609802/Clock_bmal1/1'>3D structure of CLOCK:BMAL1 heterodimer</scene> is shown in the right. It is a tightly intertwined structure where CLOCK and BMAL1 are twisted together. Although the primary sequences of CLOCK and BMAL1 are similar, the structural arrangements of their domains are quite different.<br /> <br /> ===CLOCK===<br /> <br /> <scene name='60/609802/Clock_only/1'>CLOCK</scene> is composed of three domains: one <scene name='60/609802/Clock_bhlh/1'>N-terminal bHLH</scene> domain, two PAS domains (<scene name='60/609802/Clock_psa_a/1'>PSA-A</scene> and <scene name='60/609802/Clock_psa_b/1'>PSA-B</scene>). The connections between each domain are two <scene name='60/609802/Clock_l1_l2/1'>flexible loops</scene>. Compared to the flexible loops in BMAL1, the distances of the connection loops in CLOCK are longer.<br /> <br /> ===BMAL1===<br /> <br /> <scene name='60/609802/Bmal1_only/1'>BMAL1</scene> is also composed of three domains: one <scene name='60/609802/Bmal1_bhlh/1'>N-terminal bHLH</scene> domain, two PAS domains (<scene name='60/609802/Bmal1_psa_a/1'>PSA-A</scene> and <scene name='60/609802/Bmal1_psa_b/1'>PSA-B</scene>). There is a ~15-residue flexible loop (<scene name='60/609802/Bmal1_l1/1'>L1</scene>) and a ~20-residue flexible loop (<scene name='60/609802/Bmal1_l2/1'>L2</scene>) connecting between each domain.<br /> <br /> ==The interface between CLOCK and BMAL1==<br /> <br /> In the formation of the CLOCK:BMAL1 heterodimer complex, each domain interacts with the corresponding domain of its partner subunit, i.e. CLOCK bHLH interacts with BMAL1 bHLH domain and so forth. In PSA domains, <scene name='60/609802/Clock_bmal1_psa_a/1'>both CLOCK and BMAL1 PSA-A domains</scene> contain a five-stranded antiparallel β sheet and several α helices flanking the concave surface of the sheet. In those α helices, there are two <scene name='60/609802/Clock_bmal1_a_alpha/1'>N-terminal flanking helices (A'α) externals</scene> packed in between the β-sheet faces of the two domains to mediate the heterodimeric PSA-A interactions. <br /> <br /> === PSA-A domain interface ===<br /> <br /> The interface bin the CLOCK:BMAL1 PSA-A dimer is mainly facilitated by hydrophobic interactions. Specifically, Phe104, Leu105, and Leu113 on <scene name='60/609802/Clock_bmal1_if_1/1'>the A'α helix of CLOCK contact the hydrophobic region on the β-sheet face of BMAL1</scene> (Leu159, Thr285, Tyr287, Val315, and Ile317). Similarly, Phe141, Leu142, and Leu150 on BMAL1 PSA-A contact the hydrophobic β-sheet face of CLOCK (F122, I216, V252, and T254). As a result, many residues obtained in the CLOCK:BMAL1 interface are conserved among bHLH-PAS transcription factors. This result may indicate that CLOCK and BMAL1 have a common PSA-A domain dimerization mode.<br /> <br /> ===PSA-B domain interface===<br /> <br /> The PSA-B domains of CLOCK and BMAL1 are stacked in parallel conformation. The β-sheet on PSA-B domain of BMAL1 contact the helical face of CLOCK PSA-B domain. The <scene name='60/609802/Clock_bmal1_if_2/1'>contact interface</scene> bury some hydrophobic residues on both subunits, including Try310, Val315, and Leu318 of CLOCK and Phe423, Trp427, and Val435 of BMAL1. <br /> <br /> ===The binding interface between CLOCK:BMAL1 and E-box element===<br /> <br /> [[Image:Binding.png|315 px|thumb|Fig. 1 The overlap structure of CLOCK:BMAL1 complex with bHLH Myc:Max-DNA complex (pdb: 1NKP). The figure is generated by Pymol]]<br /> <br /> As shown in Fig. 1, the four-helical bHLH bundle in the CLOCK:BMAL1 heterodimer overlaps with the bHLH Myc:Max-DNA complex (pdb: 1NKP).<br /> <br /> <br /> == The downstream effects of the altered circadian rhythm ==<br /> <br /> It has been shown in recent years that people who have lifestyles which involve light exposure that is different than the normal 12 hours of daylight/12 hours of night (such as people who work the night shift, have insomnia, often work late) have significantly increased chances of developing cancer. The circadian rhythm is partially dictated by the amount of light the organism receives so behavioral changes will causes differential activation of circadian rhythm proteins. This indicates that disruption of the normal circadian rhythm gene regulation cycle has severe downstream effects on the host's genetic makeup. Additionally, it has been shown that cancer tissues often have distorted circadian rhythms, showing the significance of circadian rhythms to cancer progression. <ref>doi: 10.1097/01.ede.0000152525.21924.54</ref><br /> <br /> Mutated forms of CLOCK exist which do not regulate protein expression correctly and thereby result in altered circadian rhythms. CLOCK-delta19 is a mutant form of CLOCK which binds to BMAL1 normally but the resulting heterodimer does not activate transcription of certain other circadian rhythm proteins. Mutant mice carrying this altered CLOCK protein have shown abnormal circadian rhythms as a result. An example of the downstream effect of this mutant form of CLOCK is the resulting abnormal expression of NAMPT. In normal mice, NAMPT is expressed in a circadian manner, showing oscillations in expression regardless of light conditions. However, in mice with mutant CLOCK-delta19, NAMPT is not expressed in an circadian manner and the overall expression is lower. This leads to further issues as NAMPT is the rate limiting enzyme for the biosynthesis of NAD+, which is an important biological coenzyme.<ref>DOI: 10.1126/science.1171641</ref><br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2071908 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-12-03T00:43:09Z

<p>Joseph Hardie: </p> <hr /> <div>==CLOCK:BMAL1 heterodimer complex==<br /> <br /> <br /> <StructureSection load='4F3L' size='340' side='right' caption='mouse CLOCK:BMAL1 heterodimer complex' scene='60/609802/Clock_bmal1/1'><br /> The <scene name='60/609802/Clock_bmal1/1'>CLOCK:BMAL1 heterodimer complex</scene> is a vital regulatory component of the circadian rhythm protein regulation system. CLOCK (''Circadian Locomotor Output Cycles Kaput'') and BMAL1 (''Brain and muscle Arnt-like protein-1'') are <scene name='60/609802/Bhlh_ex/1'>the basic helix-loop-helix</scene> PER-ARNT-SIM (bHLH-PAS) proteins. (The structure highlighted in yellow is a portion of bHLH structure in CLOCK) The CLOCK:BMAL1 heterodimer is the main transcriptional activator in the mammalian circadian mechanism.<ref>DOI: 10.1126/science.280.5369.1564</ref> The binding between CLOCK and BMAL1 involves the N-terminal bHLH, PAS-A and PAS-B domains of both proteins. Each domain (bHLH, PAS-A, PAS-B) binds to its corresponding equivalent in the other protein. Though both proteins contain the same types of domains with similar primary amino acid sequences in each, the overall heterodimer is surprisingly asymmetrical due to differences in the spatial orientation of the domains in each protein. Since this heterodimer complex involves the binding of all of the major domains in both participating proteins, the overall binding affinity is very high.<br /> <br /> == Role in Circadian Rhythm ==<br /> <br /> Circadian rhythms are operated by an endogenous core clock system that drives daily rhythms in behavior, physiology, and metabolism. In mammalian systems, the suprachiasmatic nucleus (SCN), which is located in the hypothalamus, is the locus of a master circadian clock. The SCN controls the expression of of proteins in a time dependent manner through a genetic feedback loop initiated by light passing through the eye.<ref>doi: 10.1111/ejn.12593</ref> The core molecular clockwork is composed of a transcriptional/post-translational feedback loop: CLOCK:BMAL1 (transcriptional activators) and PER:CRY (transcriptional repressors). In daytime, CLOCK and BMAL1 will form a heterodimer complex to bind the E-box promoter region of other circadian rhythm proteins, causing the transcription of Per (''Period'') and Cry (''Cryptochrome''). During the day, Per and Cry will dimerize and translocate into the nucleus, where they interact with CLOCK:BMAL1 to inhibit their own transcription, forming a negative feedback loop.<ref>DOI: 10.1126/science.1222804</ref> At night time, Per:Cry complex is degraded by a specific E3 ligase complex and the repression is relieved. After the repression level of Per:Cry is decreased, CLOCK:BMAL1 will be re-activated and start transcription again, forming the positive feedback loop. The entire negative/positive feedback loop take around 24 hours to complete, thus forming the core mechanism of the circadian clock in mammals.<ref>doi:10.1016/B978-0-12-387690-4.00006-4</ref> <br /> <br /> ==The Overall structure of CLOCK:BMAL1 complex==<br /> <br /> The <scene name='60/609802/Clock_bmal1/1'>3D structure of CLOCK:BMAL1 heterodimer</scene> is shown in the right. It is a tightly intertwined structure where CLOCK and BMAL1 are twisted together. Although the primary sequences of CLOCK and BMAL1 are similar, the structural arrangements of their domains are quite different.<br /> <br /> ===CLOCK===<br /> <br /> <scene name='60/609802/Clock_only/1'>CLOCK</scene> is composed of three domains: one <scene name='60/609802/Clock_bhlh/1'>N-terminal bHLH</scene> domain, two PAS domains (<scene name='60/609802/Clock_psa_a/1'>PSA-A</scene> and <scene name='60/609802/Clock_psa_b/1'>PSA-B</scene>). The connections between each domain are two <scene name='60/609802/Clock_l1_l2/1'>flexible loops</scene>. Compared to the flexible loops in BMAL1, the distances of the connection loops in CLOCK are longer.<br /> <br /> ===BMAL1===<br /> <br /> <scene name='60/609802/Bmal1_only/1'>BMAL1</scene> is also composed of three domains: one <scene name='60/609802/Bmal1_bhlh/1'>N-terminal bHLH</scene> domain, two PAS domains (<scene name='60/609802/Bmal1_psa_a/1'>PSA-A</scene> and <scene name='60/609802/Bmal1_psa_b/1'>PSA-B</scene>). There is a ~15-residue flexible loop (<scene name='60/609802/Bmal1_l1/1'>L1</scene>) and a ~20-residue flexible loop (<scene name='60/609802/Bmal1_l2/1'>L2</scene>) connecting between each domain.<br /> <br /> ==The interface between CLOCK and BMAL1==<br /> <br /> In the formation of the CLOCK:BMAL1 heterodimer complex, each domain interacts with the corresponding domain of its partner subunit, i.e. CLOCK bHLH interacts with BMAL1 bHLH domain and so forth. In PSA domains, <scene name='60/609802/Clock_bmal1_psa_a/1'>both CLOCK and BMAL1 PSA-A domains</scene> contain a five-stranded antiparallel β sheet and several α helices flanking the concave surface of the sheet. In those α helices, there are two <scene name='60/609802/Clock_bmal1_a_alpha/1'>N-terminal flanking helices (A'α) externals</scene> packed in between the β-sheet faces of the two domains to mediate the heterodimeric PSA-A interactions. <br /> <br /> === PSA-A domain interface ===<br /> <br /> The interface bin the CLOCK:BMAL1 PSA-A dimer is mainly facilitated by hydrophobic interactions. Specifically, Phe104, Leu105, and Leu113 on <scene name='60/609802/Clock_bmal1_if_1/1'>the A'α helix of CLOCK contact the hydrophobic region on the β-sheet face of BMAL1</scene> (Leu159, Thr285, Tyr287, Val315, and Ile317). Similarly, Phe141, Leu142, and Leu150 on BMAL1 PSA-A contact the hydrophobic β-sheet face of CLOCK (F122, I216, V252, and T254). As a result, many residues obtained in the CLOCK:BMAL1 interface are conserved among bHLH-PAS transcription factors. This result may indicate that CLOCK and BMAL1 have a common PSA-A domain dimerization mode.<br /> <br /> ===PSA-B domain interface===<br /> <br /> The PSA-B domains of CLOCK and BMAL1 are stacked in parallel conformation. The β-sheet on PSA-B domain of BMAL1 contact the helical face of CLOCK PSA-B domain. The <scene name='60/609802/Clock_bmal1_if_2/1'>contact interface</scene> bury some hydrophobic residues on both subunits, including Try310, Val315, and Leu318 of CLOCK and Phe423, Trp427, and Val435 of BMAL1. <br /> <br /> ===The binding interface between CLOCK:BMAL1 and E-box element===<br /> <br /> [[Image:Binding.png|315 px|thumb|Fig. 1 The overlap structure of CLOCK:BMAL1 complex with bHLH Myc:Max-DNA complex (pdb: 1NKP). The figure is generated by Pymol]]<br /> <br /> As shown in Fig. 1, the four-helical bHLH bundle in the CLOCK:BMAL1 heterodimer overlaps with the bHLH Myc:Max-DNA complex (pdb: 1NKP).<br /> <br /> <br /> == The downstream effects of the altered circadian rhythm ==<br /> <br /> It has been shown in recent years that people who have lifestyles which involve light exposure that is different than the normal 12 hours of daylight/12 hours of night have significantly increased chances of developing cancer. This indicates that disruption of the normal circadian rhythm gene regulation cycle has severe downstream effects on the host's genetic makeup. Additionally, it has been shown that cancer tissues often have distorted circadian rhythms, showing the significance of circadian rhythms to cancer progression. <ref>doi: 10.1097/01.ede.0000152525.21924.54</ref><br /> <br /> Mutated forms of CLOCK exist which do not regulate protein expression correctly and thereby result in altered circadian rhythms. CLOCK-delta19 is a mutant form of CLOCK which binds to BMAL1 normally but the resulting heterodimer does not activate transcription of certain other circadian rhythm proteins. Mutant mice carrying this altered CLOCK protein have shown abnormal circadian rhythms as a result. An example of the downstream effect of this mutant form of CLOCK is the resulting abnormal expression of NAMPT. In normal mice, NAMPT is expressed in a circadian manner, showing oscillations in expression regardless of light conditions. However, in mice with mutant CLOCK-delta19, NAMPT is not expressed in an circadian manner and the overall expression is lower. This leads to further issues as NAMPT is the rate limiting enzyme for the biosynthesis of NAD+, which is an important biological coenzyme.<ref>DOI: 10.1126/science.1171641</ref><br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2071907 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-12-03T00:38:38Z

<p>Joseph Hardie: </p> <hr /> <div>==CLOCK:BMAL1 heterodimer complex==<br /> <br /> <br /> <StructureSection load='4F3L' size='340' side='right' caption='mouse CLOCK:BMAL1 heterodimer complex' scene='60/609802/Clock_bmal1/1'><br /> The <scene name='60/609802/Clock_bmal1/1'>CLOCK:BMAL1 heterodimer complex</scene> is a vital regulatory component of the circadian rhythm protein regulation system. CLOCK (''Circadian Locomotor Output Cycles Kaput'') and BMAL1 (''Brain and muscle Arnt-like protein-1'') are <scene name='60/609802/Bhlh_ex/1'>the basic helix-loop-helix</scene> PER-ARNT-SIM (bHLH-PAS) proteins. (The structure highlighted in yellow is a portion of bHLH structure in CLOCK) The CLOCK:BMAL1 heterodimer is the main transcriptional activator in the mammalian circadian mechanism.<ref>DOI: 10.1126/science.280.5369.1564</ref> The binding between CLOCK and BMAL1 involves the N-terminal bHLH, PAS-A and PAS-B domains of both proteins. Each domain (bHLH, PAS-A, PAS-B) binds to its corresponding equivalent in the other protein. Though both proteins contain the same types of domains with similar primary amino acid sequences in each, the overall heterodimer is surprisingly asymmetrical due to differences in the spatial orientation of the domains in each protein. Since this heterodimer complex involves the binding of all of the major domains in both participating proteins, the overall binding affinity is very high.<br /> <br /> == Role in Circadian Rhythm ==<br /> <br /> Circadian rhythms are operated by an endogenous core clock system that drives daily rhythms in behavior, physiology, and metabolism. In mammalian systems, the suprachiasmatic nucleus (SCN), which is located in the hypothalamus, is the locus of a master circadian clock. The SCN controls the expression of of proteins in a time dependent manner through a genetic feedback loop initiated by light passing through the eye.<ref>doi: 10.1111/ejn.12593</ref> The core molecular clockwork is composed of a transcriptional/post-translational feedback loop: CLOCK:BMAL1 (transcriptional activators) and PER:CRY (transcriptional repressors). In daytime, CLOCK and BMAL1 will form a heterodimer complex to bind the E-box promoter region of other circadian rhythm proteins, causing the transcription of Per (''Period'') and Cry (''Cryptochrome''). During the day, Per and Cry will dimerize and translocate into the nucleus, where they interact with CLOCK:BMAL1 to inhibit their own transcription, forming a negative feedback loop.<ref>DOI: 10.1126/science.1222804</ref> At night time, Per:Cry complex is degraded by a specific E3 ligase complex and the repression is relieved. After the repression level of Per:Cry is decreased, CLOCK:BMAL1 will be re-activated and start transcription again, forming the positive feedback loop. The entire negative/positive feedback loop take around 24 hours to complete, thus forming the core mechanism of the circadian clock in mammals.<ref>doi:10.1016/B978-0-12-387690-4.00006-4</ref> <br /> <br /> ==The Overall structure of CLOCK:BMAL1 complex==<br /> <br /> The <scene name='60/609802/Clock_bmal1/1'>3D structure of CLOCK:BMAL1 heterodimer</scene> is shown in the right. It is a tightly intertwined structure where CLOCK and BMAL1 are twisted together. Although the primary sequences of CLOCK and BMAL1 are similar, the structural arrangements of their domains are quite different.<br /> <br /> ===CLOCK===<br /> <br /> <scene name='60/609802/Clock_only/1'>CLOCK</scene> is composed of three domains: one <scene name='60/609802/Clock_bhlh/1'>N-terminal bHLH</scene> domain, two PAS domains (<scene name='60/609802/Clock_psa_a/1'>PSA-A</scene> and <scene name='60/609802/Clock_psa_b/1'>PSA-B</scene>). The connections between each domain are two <scene name='60/609802/Clock_l1_l2/1'>flexible loops</scene>. Comparedto the flexible loops in BMAL1, the distances of the connection loops in CLOCK are longer.<br /> <br /> ===BMAL1===<br /> <br /> <scene name='60/609802/Bmal1_only/1'>BMAL1</scene> is also composed of three domains: one <scene name='60/609802/Bmal1_bhlh/1'>N-terminal bHLH</scene> domain, two PAS domains (<scene name='60/609802/Bmal1_psa_a/1'>PSA-A</scene> and <scene name='60/609802/Bmal1_psa_b/1'>PSA-B</scene>). There is a ~15-residue flexible loop (<scene name='60/609802/Bmal1_l1/1'>L1</scene>) and a ~20-residue flexible loop (<scene name='60/609802/Bmal1_l2/1'>L2</scene>) connecting between each domain.<br /> <br /> ==The interface between CLOCK and BMAL1==<br /> <br /> In the formation of the CLOCK:BMAL1 heterodimer complex, each domain interacts with the corresponding domain of its partner subunit, i.e. CLOCK bHLH interacts with BMAL1 bHLH domain and so forth. In PSA domains, <scene name='60/609802/Clock_bmal1_psa_a/1'>both CLOCK and BMAL1 PSA-A domains</scene> contain a five-stranded antiparallel β sheet and several α helices flanking the concave surface of the sheet. In those α helices, there are two <scene name='60/609802/Clock_bmal1_a_alpha/1'>N-terminal flanking helices (A'α) externals</scene> packed in between the β-sheet faces of the two domains to mediate the heterodimeric PSA-A interactions. <br /> <br /> === PSA-A domain interface ===<br /> <br /> The interface bin the CLOCK:BMAL1 PSA-A dimer is mainly facilitated by hydrophobic interactions. Specifically, Phe104, Leu105, and Leu113 on <scene name='60/609802/Clock_bmal1_if_1/1'>the A'α helix of CLOCK contact the hydrophobic region on the β-sheet face of BMAL1</scene> (Leu159, Thr285, Tyr287, Val315, and Ile317). Similarly, Phe141, Leu142, and Leu150 on BMAL1 PSA-A contact the hydrophobic β-sheet face of CLOCK (F122, I216, V252, and T254). As a result, many residues obtained in the CLOCK:BMAL1 interface are conserved among bHLH-PAS transcription factors. This result may indicate that CLOCK and BMAL1 have a common PSA-A domain dimerization mode.<br /> <br /> ===PSA-B domain interface===<br /> <br /> The PSA-B domains of CLOCK and BMAL1 are stacked in parallel conformation. The β-sheet on PSA-B domain of BMAL1 contact the helical face of CLOCK PSA-B domain. The <scene name='60/609802/Clock_bmal1_if_2/1'>contact interface</scene> bury some hydrophobic residues on both subunits, including Try310, Val315, and Leu318 of CLOCK and Phe423, Trp427, and Val435 of BMAL1. <br /> <br /> ===The binding interface between CLOCK:BMAL1 and E-box element===<br /> <br /> [[Image:Binding.png|315 px|thumb|Fig. 1 The overlap structure of CLOCK:BMAL1 complex with bHLH Myc:Max-DNA complex (pdb: 1NKP). The figure is generated by Pymol]]<br /> <br /> As shown in Fig. 1, the four-helical bHLH bundle in the CLOCK:BMAL1 heterodimer overlaps with the bHLH Myc:Max-DNA complex (pdb: 1NKP).<br /> <br /> <br /> == The downstream effects of the altered circadian rhythm ==<br /> <br /> It has been shown in recent years that people who have lifestyles which involve light exposure that is different than the normal 12 hours of daylight/12 hours of night have significantly increased chances of developing cancer. This indicates that disruption of the normal circadian rhythm gene regulation cycle has severe downstream effects on the host's genetic makeup. Additionally, it has been shown that cancer tissues often have distorted circadian rhythms, showing the significance of circadian rhythms to cancer progression. <ref>doi: 10.1097/01.ede.0000152525.21924.54</ref><br /> <br /> Mutated forms of CLOCK exist which do not regulate protein expression correctly and thereby result in altered circadian rhythms. CLOCK-delta19 is a mutant form of CLOCK which binds to BMAL1 normally but the resulting heterodimer does not activate transcription of certain other circadian rhythm proteins. Mutant mice carrying this altered CLOCK protein have shown abnormal circadian rhythms as a result. An example of the downstream effect of this mutant form of CLOCK is the resulting abnormal expression of NAMPT. In normal mice, NAMPT is expressed in a circadian manner, showing oscillations in expression regardless of light conditions. However, in mice with mutant CLOCK-delta19, NAMPT is not expressed in an circadian manner and the overall expression is lower. This leads to further issues as NAMPT is the rate limiting enzyme for the biosynthesis of NAD+, which is an important biological coenzyme.<ref>DOI: 10.1126/science.1171641</ref><br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2071901 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-12-03T00:17:18Z

<p>Joseph Hardie: </p> <hr /> <div>==CLOCK:BMAL1 heterodimer complex==<br /> <br /> <br /> <StructureSection load='4F3L' size='340' side='right' caption='mouse CLOCK:BMAL1 heterodimer complex' scene='60/609802/Clock_bmal1/1'><br /> The <scene name='60/609802/Clock_bmal1/1'>CLOCK:BMAL1 heterodimer complex</scene> is a vital regulatory component of the circadian rhythm protein regulation system. CLOCK (''Circadian Locomotor Output Cycles Kaput'') and BMAL1 (''Brain and muscle Arnt-like protein-1'') are <scene name='60/609802/Bhlh_ex/1'>the basic helix-loop-helix</scene> PER-ARNT-SIM (bHLH-PAS) proteins. (The structure highlighted in yellow is a portion of bHLH structure in CLOCK) The CLOCK:BMAL1 heterodimer is the main transcriptional activator in the mammalian circadian mechanism.<ref>DOI: 10.1126/science.280.5369.1564</ref> The binding between CLOCK and BMAL1 involves the N-terminal bHLH, PAS-A and PAS-B domains of both proteins. Each domain (bHLH, PAS-A, PAS-B) binds to its corresponding equivalent in the other protein. Though both proteins contain the same types of domains with similar primary amino acid sequences in each, the overall heterodimer is surprisingly asymmetrical due to differences in the spatial orientation of the domains in each protein. Since this heterodimer complex involves the binding of all of the major domains in both participating proteins, the overall binding affinity is very high.<br /> <br /> == Role in Circadian Rhythm ==<br /> <br /> Circadian rhythms are operated by an endogenous core clock system that drives daily rhythms in behavior, physiology, and metabolism. In mammalian systems, the suprachiasmatic nucleus (SCN), which is located in the hypothalamus, is the locus of a master circadian clock. The SCN controls the expression of of proteins in a time dependent manner through a genetic feedback loop initiated by light passing through the eye.<ref>doi: 10.1111/ejn.12593</ref> The core molecular clockwork is composed of a transcriptional/post-translational feedback loop: CLOCK:BMAL1 (transcriptional activators) and PER:CRY (transcriptional repressors). In daytime, CLOCK and BMAL1 will form a heterodimer complex to bind the E-box promoter region of other circadian rhythm proteins, causing the transcription of Per (''Period'') and Cry (''Cryptochrome''). During the day, Per and Cry will dimerize and translocate into the nucleus, where they interact with CLOCK:BMAL1 to inhibit their own transcription, forming a negative feedback loop.<ref>DOI: 10.1126/science.1222804</ref> At night time, Per:Cry complex is degraded by a specific E3 ligase complex and the repression is relieved. After the repression level of Per:Cry is decreased, CLOCK:BMAL1 will be re-activated and start transcription again. This process is called the positive feedback loop. The whole negative/positive feedback loops take around 24 h to complete, thus form the core mechanism of the circadian clock in mammals.<ref>doi:10.1016/B978-0-12-387690-4.00006-4</ref> <br /> <br /> ==The Overall structure of CLOCK:BMAL1 complex==<br /> <br /> The <scene name='60/609802/Clock_bmal1/1'>3D structure of CLOCK:BMAL1 heterodimer</scene> is shown in the right. It is a tightly interwined structure that CLOCK and BMAL1 are twisted together. Although the primary sequences of CLOCK and BMAL1 are similar, the structural arrangements of their domains are quite different.<br /> <br /> ===CLOCK===<br /> <br /> <scene name='60/609802/Clock_only/1'>CLOCK</scene> is composed of three domains: one <scene name='60/609802/Clock_bhlh/1'>N-terminal bHLH</scene> domain, two PAS domains (<scene name='60/609802/Clock_psa_a/1'>PSA-A</scene> and <scene name='60/609802/Clock_psa_b/1'>PSA-B</scene>). The connections between each domain are two <scene name='60/609802/Clock_l1_l2/1'>flexible loops</scene>. Comparing to the flexible loops in BMAL1, the distances of the connection loops in CLOCK are longer.<br /> <br /> ===BMAL1===<br /> <br /> <scene name='60/609802/Bmal1_only/1'>BMAL1</scene> is also composed of three domains: one <scene name='60/609802/Bmal1_bhlh/1'>N-terminal bHLH</scene> domain, two PAS domains (<scene name='60/609802/Bmal1_psa_a/1'>PSA-A</scene> and <scene name='60/609802/Bmal1_psa_b/1'>PSA-B</scene>). There are ~15-residue flexible loop (<scene name='60/609802/Bmal1_l1/1'>L1</scene>) and ~20-residue flexible loop (<scene name='60/609802/Bmal1_l2/1'>L2</scene>) connect between each domains.<br /> <br /> ==The interface between CLOCK and BMAL1==<br /> <br /> In the formation of CLOCK:BMAL1 heterodimer complex, each domain interacts with the corresponding domain of its partner subunit, which means CLOCK bHLH interacts with BMAL1 bHLH domain, CLOCK PSA-A interacts with BMAL1 PSA-A domain, and CLOCK PSA-B interacts with BMAL1 PSA-B domain. In PSA domains, <scene name='60/609802/Clock_bmal1_psa_a/1'>both CLOCK and BMAL1 PSA-A domains</scene> contain five-stranded antiparallel β sheet and several α helices flanking the concave surface of the sheet. In those α helices, there are two <scene name='60/609802/Clock_bmal1_a_alpha/1'>N-terminal flanking helix (A'α) externals</scene> pack in between the β-sheet faces of two domains to mediate the heterodimeric PSA-A interactions. <br /> <br /> === PSA-A domain interface ===<br /> <br /> The interface between CLOCK:BMAL1 PSA-A dimer is mainly facilitated by hydrophobic interactions. Specifically, Phe104, Leu105, and Leu113 on <scene name='60/609802/Clock_bmal1_if_1/1'>the A'α helix of CLOCK contact the hydrophobic region on the β-sheet face of BMAL1</scene> (Leu159, Thr285, Tyr287, Val315, and Ile317). Similarly, Phe141, Leu142, and Leu150 on BMAL1 PSA-A contact to the hydrophobic β-sheet face of CLOCK (F122, I216, V252, and T254). As a result, many residues obtained in the CLOCK:BMAL1 interface are conserved among bHLH-PAS transcription factors. This result may indicate that CLOCK and BMAL1 have a common PSA-A domain dimerization mode.<br /> <br /> ===PSA-B domain interface===<br /> <br /> The PSA-B domains of CLOCK and BMAL1 are stacked in parallel conformation. The β-sheet on PSA-B domain of BMAL1 contacts with the helical face of CLOCK PSA-B domain. The <scene name='60/609802/Clock_bmal1_if_2/1'>contact interface</scene> bury some hydrophobic residues on both subunits, including Try310, Val315, and Leu318 of CLOCK and Phe423, Trp427, and Val435 of BMAL1. <br /> <br /> ===The binding interface between CLOCK:BMAL1 and E-box element===<br /> <br /> <br /> <br /> <br /> == The downstream effects of the altered circadian rhythm ==<br /> <br /> It has been shown in recent years that people who have lifestyles which involve light exposure that is different than the normal 12 hours of daylight/12 hours of night have significantly increased chances of developing cancer. This indicates that disruption of the normal circadian rhythm gene regulation cycle has severe downstream effects on the host's genetic makeup. Additionally, it has been shown that cancer tissues often have distorted circadian rhythms, showing the significance of circadian rhythms to cancer progression. <ref>doi: 10.1097/01.ede.0000152525.21924.54</ref><br /> <br /> Mutated forms of CLOCK exist which do not regulate protein expression correctly and thereby result in altered circadian rhythms. CLOCK-delta19 is a mutant form of CLOCK which binds to BMAL1 normally but the resulting heterodimer does not activate transcription of certain other circadian rhythm proteins. Mutant mice carrying this altered CLOCK protein have shown abnormal circadian rhythms as a result. An example of the downstream effect of this mutant form of CLOCK is the resulting abnormal expression of NAMPT. In normal mice, NAMPT is expressed in a circadian manner, showing oscillations in expression regardless of light conditions. However, in mice with mutant CLOCK-delta19, NAMPT is not expressed in an circadian manner and the overall expression is lower. This leads to further issues as NAMPT is the rate limiting enzyme for the biosynthesis of NAD+, which is an important biological coenzyme.<ref>DOI: 10.1126/science.1171641</ref><br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2071899 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-12-03T00:09:05Z

<p>Joseph Hardie: </p> <hr /> <div>==CLOCK:BMAL1 heterodimer complex==<br /> <br /> <br /> <StructureSection load='4F3L' size='340' side='right' caption='mouse CLOCK:BMAL1 heterodimer complex' scene='60/609802/Clock_bmal1/1'><br /> The <scene name='60/609802/Clock_bmal1/1'>CLOCK:BMAL1 heterodimer complex</scene> is a vital regulatory component of the circadian rhythm protein regulation system. CLOCK (''Circadian Locomotor Output Cycles Kaput'') and BMAL1 (''Brain and muscle Arnt-like protein-1'') are <scene name='60/609802/Bhlh_ex/1'>the basic helix-loop-helix</scene> PER-ARNT-SIM (bHLH-PAS) proteins. (The structure highlighted in yellow is a portion of bHLH structure in CLOCK) The CLOCK:BMAL1 heterodimer is the main transcriptional activator in the mammalian circadian mechanism.<ref>DOI: 10.1126/science.280.5369.1564</ref> The binding between CLOCK and BMAL1 involves the N-terminal bHLH, PAS-A and PAS-B domains of both proteins. Each domain (bHLH, PAS-A, PAS-B) binds to its corresponding equivalent in the other protein. Though both proteins contain the same types of domains with similar primary amino acid sequences in each, the overall heterodimer is surprisingly asymmetrical due to differences in the spatial orientation of the domains in each protein. Since this heterodimer complex involves the binding of all of the major domains in both participating proteins, the overall binding affinity is very high.<br /> <br /> == Role in Circadian Rhythm ==<br /> <br /> Circadian rhythms are operated by an endogenous core clock system that drives daily rhythms in behavior, physiology, and metabolism. In mammalian systems, the suprachiasmatic nucleus (SCN), which is located in the hypothalamus, is the locus of a master circadian clock. The SCN controls the expression of of proteins in a time dependent manner through a genetic feedback loop initiated by light passing through the eye.<ref>doi: 10.1111/ejn.12593</ref> The core molecular clockwork is composed of a transcriptional/post-translational feedback loop: CLOCK:BMAL1 (transcriptional activators) and PER:CRY (transcriptional repressors). In daytime, CLOCK and BMAL1 will form a heterodimer complex and binds to the E-box promoter region of other circadian rhythm proteins, following by the initiation of the transcription of Per (''Period'') and Cry (''Cryptochrome''). During the day, Per and Cry will dimerize and translocate into the nucleus, where they interact with CLOCK:BMAL1 to inhibit their own transcription. This process is called the negative feedback loop.<ref>DOI: 10.1126/science.1222804</ref> At night time, Per:Cry complex is degradated by a specific E3 ligase complex and the repression will be relieved. After the repression level of Per:Cry is decreased, CLOCK:BMAL1 will be re-activated and start a new transcription. This process is called the positive feedback loop. The whole negative/positive feedback loops take around 24 h to complete, thus form the core mechanism of the circadian clock in mammals.<ref>doi:10.1016/B978-0-12-387690-4.00006-4</ref> <br /> <br /> ==The Overall structure of CLOCK:BMAL1 complex==<br /> <br /> The <scene name='60/609802/Clock_bmal1/1'>3D structure of CLOCK:BMAL1 heterodimer</scene> is shown in the right. It is a tightly interwined structure that CLOCK and BMAL1 are twisted together. Although the primary sequences of CLOCK and BMAL1 are similar, the structural arrangements of their domains are quite different.<br /> <br /> ===CLOCK===<br /> <br /> <scene name='60/609802/Clock_only/1'>CLOCK</scene> is composed of three domains: one <scene name='60/609802/Clock_bhlh/1'>N-terminal bHLH</scene> domain, two PAS domains (<scene name='60/609802/Clock_psa_a/1'>PSA-A</scene> and <scene name='60/609802/Clock_psa_b/1'>PSA-B</scene>). The connections between each domain are two <scene name='60/609802/Clock_l1_l2/1'>flexible loops</scene>. Comparing to the flexible loops in BMAL1, the distances of the connection loops in CLOCK are longer.<br /> <br /> ===BMAL1===<br /> <br /> <scene name='60/609802/Bmal1_only/1'>BMAL1</scene> is also composed of three domains: one <scene name='60/609802/Bmal1_bhlh/1'>N-terminal bHLH</scene> domain, two PAS domains (<scene name='60/609802/Bmal1_psa_a/1'>PSA-A</scene> and <scene name='60/609802/Bmal1_psa_b/1'>PSA-B</scene>). There are ~15-residue flexible loop (<scene name='60/609802/Bmal1_l1/1'>L1</scene>) and ~20-residue flexible loop (<scene name='60/609802/Bmal1_l2/1'>L2</scene>) connect between each domains.<br /> <br /> ==The interface between CLOCK and BMAL1==<br /> <br /> In the formation of CLOCK:BMAL1 heterodimer complex, each domain interacts with the corresponding domain of its partner subunit, which means CLOCK bHLH interacts with BMAL1 bHLH domain, CLOCK PSA-A interacts with BMAL1 PSA-A domain, and CLOCK PSA-B interacts with BMAL1 PSA-B domain. In PSA domains, <scene name='60/609802/Clock_bmal1_psa_a/1'>both CLOCK and BMAL1 PSA-A domains</scene> contain five-stranded antiparallel β sheet and several α helices flanking the concave surface of the sheet. In those α helices, there are two <scene name='60/609802/Clock_bmal1_a_alpha/1'>N-terminal flanking helix (A'α) externals</scene> pack in between the β-sheet faces of two domains to mediate the heterodimeric PSA-A interactions. <br /> <br /> === PSA-A domain interface ===<br /> <br /> The interface between CLOCK:BMAL1 PSA-A dimer is mainly facilitated by hydrophobic interactions. Specifically, Phe104, Leu105, and Leu113 on <scene name='60/609802/Clock_bmal1_if_1/1'>the A'α helix of CLOCK contact the hydrophobic region on the β-sheet face of BMAL1</scene> (Leu159, Thr285, Tyr287, Val315, and Ile317). Similarly, Phe141, Leu142, and Leu150 on BMAL1 PSA-A contact to the hydrophobic β-sheet face of CLOCK (F122, I216, V252, and T254). As a result, many residues obtained in the CLOCK:BMAL1 interface are conserved among bHLH-PAS transcription factors. This result may indicate that CLOCK and BMAL1 have a common PSA-A domain dimerization mode.<br /> <br /> ===PSA-B domain interface===<br /> <br /> The PSA-B domains of CLOCK and BMAL1 are stacked in parallel conformation. The β-sheet on PSA-B domain of BMAL1 contacts with the helical face of CLOCK PSA-B domain. The <scene name='60/609802/Clock_bmal1_if_2/1'>contact interface</scene> bury some hydrophobic residues on both subunits, including Try310, Val315, and Leu318 of CLOCK and Phe423, Trp427, and Val435 of BMAL1. <br /> <br /> ===The binding interface between CLOCK:BMAL1 and E-box element===<br /> <br /> <br /> <br /> <br /> == The downstream effects of the altered circadian rhythm ==<br /> <br /> It has been shown in recent years that people who have lifestyles which involve light exposure that is different than the normal 12 hours of daylight/12 hours of night have significantly increased chances of developing cancer. This indicates that disruption of the normal circadian rhythm gene regulation cycle has severe downstream effects on the host's genetic makeup. Additionally, it has been shown that cancer tissues often have distorted circadian rhythms, showing the significance of circadian rhythms to cancer progression. <ref>doi: 10.1097/01.ede.0000152525.21924.54</ref><br /> <br /> Mutated forms of CLOCK exist which do not regulate protein expression correctly and thereby result in altered circadian rhythms. CLOCK-delta19 is a mutant form of CLOCK which binds to BMAL1 normally but the resulting heterodimer does not activate transcription of certain other circadian rhythm proteins. Mutant mice carrying this altered CLOCK protein have shown abnormal circadian rhythms as a result. An example of the downstream effect of this mutant form of CLOCK is the resulting abnormal expression of NAMPT. In normal mice, NAMPT is expressed in a circadian manner, showing oscillations in expression regardless of light conditions. However, in mice with mutant CLOCK-delta19, NAMPT is not expressed in an circadian manner and the overall expression is lower. This leads to further issues as NAMPT is the rate limiting enzyme for the biosynthesis of NAD+, which is an important biological coenzyme.<ref>DOI: 10.1126/science.1171641</ref><br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2071898 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-12-03T00:04:52Z

<p>Joseph Hardie: </p> <hr /> <div>==CLOCK:BMAL1 heterodimer complex==<br /> <br /> <br /> <StructureSection load='4F3L' size='340' side='right' caption='mouse CLOCK:BMAL1 heterodimer complex' scene='60/609802/Clock_bmal1/1'><br /> The <scene name='60/609802/Clock_bmal1/1'>CLOCK:BMAL1 heterodimer complex</scene> is a vital regulatory component of the circadian rhythm protein regulation system. CLOCK (''Circadian Locomotor Output Cycles Kaput'') and BMAL1 (''Brain and muscle Arnt-like protein-1'') are <scene name='60/609802/Bhlh_ex/1'>the basic helix-loop-helix</scene> PER-ARNT-SIM (bHLH-PAS) proteins. The structure highlighted in yellow is a portion of bHLH structure in CLOCK. The CLOCK:BMAL1 heterodimer is the main transcriptional activator in the mammalian circadian mechanism.<ref>DOI: 10.1126/science.280.5369.1564</ref> The binding between CLOCK and BMAL1 involves the N-terminal bHLH, PAS-A and PAS-B domains of both proteins. Each domain binds to its corresponding equivalent domain in the other protein. Though both proteins contain the same types of domains with similar primary amino acid sequences in each, the overall heterodimer is surprisingly asymmetrical due to differences in the spatial orientation of the domains in each protein. Since this heterodimer complex involves the binding of all of the major domains in both participating proteins, the overall binding affinity is very high.<br /> <br /> == Role in Circadian Rhythm ==<br /> <br /> Circadian rhythms are operated by an endogenous core clock system that drives daily rhythms in behavior, physiology, and metabolism. In mammalian systems, the suprachiasmatic nucleus (SCN), which is located in the hypothalamus, is the locus of a master circadian clock. The SCN controls the expression of of proteins in a time dependent manner through a genetic feedback loop initiated by light passing through the eye.<ref>doi: 10.1111/ejn.12593</ref> The core molecular clockwork is composed of a transcriptional/post-translational feedback loop: CLOCK:BMAL1 (transcriptional activators) and PER:CRY (transcriptional repressors). In daytime, CLOCK and BMAL1 will form a heterodimer complex and binds to the E-box promoter region of other circadian rhythm proteins, following by the initiation of the transcription of Per (''Period'') and Cry (''Cryptochrome''). During the day, Per and Cry will dimerize and translocate into the nucleus, where they interact with CLOCK:BMAL1 to inhibit their own transcription. This process is called the negative feedback loop.<ref>DOI: 10.1126/science.1222804</ref> At night time, Per:Cry complex is degradated by a specific E3 ligase complex and the repression will be relieved. After the repression level of Per:Cry is decreased, CLOCK:BMAL1 will be re-activated and start a new transcription. This process is called the positive feedback loop. The whole negative/positive feedback loops take around 24 h to complete, thus form the core mechanism of the circadian clock in mammals.<ref>doi:10.1016/B978-0-12-387690-4.00006-4</ref> <br /> <br /> ==The Overall structure of CLOCK:BMAL1 complex==<br /> <br /> The <scene name='60/609802/Clock_bmal1/1'>3D structure of CLOCK:BMAL1 heterodimer</scene> is shown in the right. It is a tightly interwined structure that CLOCK and BMAL1 are twisted together. Although the primary sequences of CLOCK and BMAL1 are similar, the structural arrangements of their domains are quite different.<br /> <br /> ===CLOCK===<br /> <br /> <scene name='60/609802/Clock_only/1'>CLOCK</scene> is composed of three domains: one <scene name='60/609802/Clock_bhlh/1'>N-terminal bHLH</scene> domain, two PAS domains (<scene name='60/609802/Clock_psa_a/1'>PSA-A</scene> and <scene name='60/609802/Clock_psa_b/1'>PSA-B</scene>). The connections between each domain are two <scene name='60/609802/Clock_l1_l2/1'>flexible loops</scene>. Comparing to the flexible loops in BMAL1, the distances of the connection loops in CLOCK are longer.<br /> <br /> ===BMAL1===<br /> <br /> <scene name='60/609802/Bmal1_only/1'>BMAL1</scene> is also composed of three domains: one <scene name='60/609802/Bmal1_bhlh/1'>N-terminal bHLH</scene> domain, two PAS domains (<scene name='60/609802/Bmal1_psa_a/1'>PSA-A</scene> and <scene name='60/609802/Bmal1_psa_b/1'>PSA-B</scene>). There are ~15-residue flexible loop (<scene name='60/609802/Bmal1_l1/1'>L1</scene>) and ~20-residue flexible loop (<scene name='60/609802/Bmal1_l2/1'>L2</scene>) connect between each domains.<br /> <br /> ==The interface between CLOCK and BMAL1==<br /> <br /> In the formation of CLOCK:BMAL1 heterodimer complex, each domain interacts with the corresponding domain of its partner subunit, which means CLOCK bHLH interacts with BMAL1 bHLH domain, CLOCK PSA-A interacts with BMAL1 PSA-A domain, and CLOCK PSA-B interacts with BMAL1 PSA-B domain. In PSA domains, <scene name='60/609802/Clock_bmal1_psa_a/1'>both CLOCK and BMAL1 PSA-A domains</scene> contain five-stranded antiparallel β sheet and several α helices flanking the concave surface of the sheet. In those α helices, there are two <scene name='60/609802/Clock_bmal1_a_alpha/1'>N-terminal flanking helix (A'α) externals</scene> pack in between the β-sheet faces of two domains to mediate the heterodimeric PSA-A interactions. <br /> <br /> === PSA-A domain interface ===<br /> <br /> The interface between CLOCK:BMAL1 PSA-A dimer is mainly facilitated by hydrophobic interactions. Specifically, Phe104, Leu105, and Leu113 on <scene name='60/609802/Clock_bmal1_if_1/1'>the A'α helix of CLOCK contact the hydrophobic region on the β-sheet face of BMAL1</scene> (Leu159, Thr285, Tyr287, Val315, and Ile317). Similarly, Phe141, Leu142, and Leu150 on BMAL1 PSA-A contact to the hydrophobic β-sheet face of CLOCK (F122, I216, V252, and T254). As a result, many residues obtained in the CLOCK:BMAL1 interface are conserved among bHLH-PAS transcription factors. This result may indicate that CLOCK and BMAL1 have a common PSA-A domain dimerization mode.<br /> <br /> ===PSA-B domain interface===<br /> <br /> The PSA-B domains of CLOCK and BMAL1 are stacked in parallel conformation. The β-sheet on PSA-B domain of BMAL1 contacts with the helical face of CLOCK PSA-B domain. The <scene name='60/609802/Clock_bmal1_if_2/1'>contact interface</scene> bury some hydrophobic residues on both subunits, including Try310, Val315, and Leu318 of CLOCK and Phe423, Trp427, and Val435 of BMAL1. <br /> <br /> ===The binding interface between CLOCK:BMAL1 and E-box element===<br /> <br /> <br /> <br /> <br /> == The downstream effects of the altered circadian rhythm ==<br /> <br /> It has been shown in recent years that people who have lifestyles which involve light exposure that is different than the normal 12 hours of daylight/12 hours of night have significantly increased chances of developing cancer. This indicates that disruption of the normal circadian rhythm gene regulation cycle has severe downstream effects on the host's genetic makeup. Additionally, it has been shown that cancer tissues often have distorted circadian rhythms, showing the significance of circadian rhythms to cancer progression. <ref>doi: 10.1097/01.ede.0000152525.21924.54</ref><br /> <br /> Mutated forms of CLOCK exist which do not regulate protein expression correctly and thereby result in altered circadian rhythms. CLOCK-delta19 is a mutant form of CLOCK which binds to BMAL1 normally but the resulting heterodimer does not activate transcription of certain other circadian rhythm proteins. Mutant mice carrying this altered CLOCK protein have shown abnormal circadian rhythms as a result. An example of the downstream effect of this mutant form of CLOCK is the resulting abnormal expression of NAMPT. In normal mice, NAMPT is expressed in a circadian manner, showing oscillations in expression regardless of light conditions. However, in mice with mutant CLOCK-delta19, NAMPT is not expressed in an circadian manner and the overall expression is lower. This leads to further issues as NAMPT is the rate limiting enzyme for the biosynthesis of NAD+, which is an important biological coenzyme.<ref>DOI: 10.1126/science.1171641</ref><br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2071897 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-12-03T00:03:21Z

<p>Joseph Hardie: </p> <hr /> <div>==CLOCK:BMAL1 heterodimer complex==<br /> <br /> <br /> <StructureSection load='4F3L' size='340' side='right' caption='mouse CLOCK:BMAL1 heterodimer complex' scene='60/609802/Clock_bmal1/1'><br /> The <scene name='60/609802/Clock_bmal1/1'>CLOCK:BMAL1 heterodimer complex</scene> is a vital regulatory component of the circadian rhythm protein regulation system. CLOCK (''Circadian Locomotor Output Cycles Kaput'') and BMAL1 (''Brain and muscle Arnt-like protein-1'') are <scene name='60/609802/Bhlh_ex/1'>the basic helix-loop-helix</scene> PER-ARNT-SIM (bHLH-PAS) proteins. The structure highlighted in yellow is a portion of bHLH structure in CLOCK. They are the main transcriptional activators in the mammalian circadian mechanism.<ref>DOI: 10.1126/science.280.5369.1564</ref> The binding between CLOCK and BMAL1 involves the N-terminal bHLH, PAS-A and PAS-B domains of both proteins. Each domain binds to its corresponding equivalent domain in the other protein. Though both proteins contain the same types of domains with similar primary amino acid sequences in each, the overall heterodimer is surprisingly asymmetrical due to differences in the spatial orientation of the domains in each protein. Since this heterodimer complex involves the binding of all of the major domains in both participating proteins, the overall binding affinity is very high.<br /> <br /> == Role in Circadian Rhythm ==<br /> <br /> Circadian rhythms are operated by an endogenous core clock system that drives daily rhythms in behavior, physiology, and metabolism. In mammalian systems, the suprachiasmatic nucleus (SCN), which is located in the hypothalamus, is the locus of a master circadian clock. The SCN controls the expression of of proteins in a time dependent manner through a genetic feedback loop initiated by light passing through the eye.<ref>doi: 10.1111/ejn.12593</ref> The core molecular clockwork is composed of a transcriptional/post-translational feedback loop: CLOCK:BMAL1 (transcriptional activators) and PER:CRY (transcriptional repressors). In daytime, CLOCK and BMAL1 will form a heterodimer complex and binds to the E-box promoter region of other circadian rhythm proteins, following by the initiation of the transcription of Per (''Period'') and Cry (''Cryptochrome''). During the day, Per and Cry will dimerize and translocate into the nucleus, where they interact with CLOCK:BMAL1 to inhibit their own transcription. This process is called the negative feedback loop.<ref>DOI: 10.1126/science.1222804</ref> At night time, Per:Cry complex is degradated by a specific E3 ligase complex and the repression will be relieved. After the repression level of Per:Cry is decreased, CLOCK:BMAL1 will be re-activated and start a new transcription. This process is called the positive feedback loop. The whole negative/positive feedback loops take around 24 h to complete, thus form the core mechanism of the circadian clock in mammals.<ref>doi:10.1016/B978-0-12-387690-4.00006-4</ref> <br /> <br /> ==The Overall structure of CLOCK:BMAL1 complex==<br /> <br /> The <scene name='60/609802/Clock_bmal1/1'>3D structure of CLOCK:BMAL1 heterodimer</scene> is shown in the right. It is a tightly interwined structure that CLOCK and BMAL1 are twisted together. Although the primary sequences of CLOCK and BMAL1 are similar, the structural arrangements of their domains are quite different.<br /> <br /> ===CLOCK===<br /> <br /> <scene name='60/609802/Clock_only/1'>CLOCK</scene> is composed of three domains: one <scene name='60/609802/Clock_bhlh/1'>N-terminal bHLH</scene> domain, two PAS domains (<scene name='60/609802/Clock_psa_a/1'>PSA-A</scene> and <scene name='60/609802/Clock_psa_b/1'>PSA-B</scene>). The connections between each domain are two <scene name='60/609802/Clock_l1_l2/1'>flexible loops</scene>. Comparing to the flexible loops in BMAL1, the distances of the connection loops in CLOCK are longer.<br /> <br /> ===BMAL1===<br /> <br /> <scene name='60/609802/Bmal1_only/1'>BMAL1</scene> is also composed of three domains: one <scene name='60/609802/Bmal1_bhlh/1'>N-terminal bHLH</scene> domain, two PAS domains (<scene name='60/609802/Bmal1_psa_a/1'>PSA-A</scene> and <scene name='60/609802/Bmal1_psa_b/1'>PSA-B</scene>). There are ~15-residue flexible loop (<scene name='60/609802/Bmal1_l1/1'>L1</scene>) and ~20-residue flexible loop (<scene name='60/609802/Bmal1_l2/1'>L2</scene>) connect between each domains.<br /> <br /> ==The interface between CLOCK and BMAL1==<br /> <br /> In the formation of CLOCK:BMAL1 heterodimer complex, each domain interacts with the corresponding domain of its partner subunit, which means CLOCK bHLH interacts with BMAL1 bHLH domain, CLOCK PSA-A interacts with BMAL1 PSA-A domain, and CLOCK PSA-B interacts with BMAL1 PSA-B domain. In PSA domains, <scene name='60/609802/Clock_bmal1_psa_a/1'>both CLOCK and BMAL1 PSA-A domains</scene> contain five-stranded antiparallel β sheet and several α helices flanking the concave surface of the sheet. In those α helices, there are two <scene name='60/609802/Clock_bmal1_a_alpha/1'>N-terminal flanking helix (A'α) externals</scene> pack in between the β-sheet faces of two domains to mediate the heterodimeric PSA-A interactions. <br /> <br /> === PSA-A domain interface ===<br /> <br /> The interface between CLOCK:BMAL1 PSA-A dimer is mainly facilitated by hydrophobic interactions. Specifically, Phe104, Leu105, and Leu113 on <scene name='60/609802/Clock_bmal1_if_1/1'>the A'α helix of CLOCK contact the hydrophobic region on the β-sheet face of BMAL1</scene> (Leu159, Thr285, Tyr287, Val315, and Ile317). Similarly, Phe141, Leu142, and Leu150 on BMAL1 PSA-A contact to the hydrophobic β-sheet face of CLOCK (F122, I216, V252, and T254). As a result, many residues obtained in the CLOCK:BMAL1 interface are conserved among bHLH-PAS transcription factors. This result may indicate that CLOCK and BMAL1 have a common PSA-A domain dimerization mode.<br /> <br /> ===PSA-B domain interface===<br /> <br /> The PSA-B domains of CLOCK and BMAL1 are stacked in parallel conformation. The β-sheet on PSA-B domain of BMAL1 contacts with the helical face of CLOCK PSA-B domain. The <scene name='60/609802/Clock_bmal1_if_2/1'>contact interface</scene> bury some hydrophobic residues on both subunits, including Try310, Val315, and Leu318 of CLOCK and Phe423, Trp427, and Val435 of BMAL1. <br /> <br /> ===The binding interface between CLOCK:BMAL1 and E-box element===<br /> <br /> <br /> <br /> <br /> == The downstream effects of the altered circadian rhythm ==<br /> <br /> It has been shown in recent years that people who have lifestyles which involve light exposure that is different than the normal 12 hours of daylight/12 hours of night have significantly increased chances of developing cancer. This indicates that disruption of the normal circadian rhythm gene regulation cycle has severe downstream effects on the host's genetic makeup. Additionally, it has been shown that cancer tissues often have distorted circadian rhythms, showing the significance of circadian rhythms to cancer progression. <ref>doi: 10.1097/01.ede.0000152525.21924.54</ref><br /> <br /> Mutated forms of CLOCK exist which do not regulate protein expression correctly and thereby result in altered circadian rhythms. CLOCK-delta19 is a mutant form of CLOCK which binds to BMAL1 normally but the resulting heterodimer does not activate transcription of certain other circadian rhythm proteins. Mutant mice carrying this altered CLOCK protein have shown abnormal circadian rhythms as a result. An example of the downstream effect of this mutant form of CLOCK is the resulting abnormal expression of NAMPT. In normal mice, NAMPT is expressed in a circadian manner, showing oscillations in expression regardless of light conditions. However, in mice with mutant CLOCK-delta19, NAMPT is not expressed in an circadian manner and the overall expression is lower. This leads to further issues as NAMPT is the rate limiting enzyme for the biosynthesis of NAD+, which is an important biological coenzyme.<ref>DOI: 10.1126/science.1171641</ref><br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2071896 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-12-03T00:01:52Z

<p>Joseph Hardie: </p> <hr /> <div>==CLOCK:BMAL1 heterodimer complex==<br /> <br /> <br /> <StructureSection load='4F3L' size='340' side='right' caption='mouse CLOCK:BMAL1 heterodimer complex' scene='60/609802/Clock_bmal1/1'><br /> The <scene name='60/609802/Clock_bmal1/1'>CLOCK:BMAL1 heterodimer complex</scene> is a vital regulatory component of the circadian rhythm protein regulation system. CLOCK (''Circadian Locomotor Output Cycles Kaput'') and BMAL1 (''Brain and muscle Arnt-like protein-1'') are <scene name='60/609802/Bhlh_ex/1'>the basic helix-loop-helix</scene> PER-ARNT-SIM (bHLH-PAS) proteins (The structure highlighted in yellow is just a portion of bHLH structure in CLOCK). They are the main transcriptional activators in the mammalian circadian mechanism.<ref>DOI: 10.1126/science.280.5369.1564</ref> The binding between CLOCK and BMAL1 involves the N-terminal bHLH, PAS-A and PAS-B domains of both proteins. Each domain binds to its corresponding equivalent domain in the other protein. Though both proteins contain the same types of domains with similar primary amino acid sequences in each, the overall heterodimer is surprisingly asymmetrical due to differences in the spatial orientation of the domains in each protein. Since this heterodimer complex involves the binding of all of the major domains in both participating proteins, the overall binding affinity is very high.<br /> <br /> == Role in Circadian Rhythm ==<br /> <br /> Circadian rhythms are operated by an endogenous core clock system that drives daily rhythms in behavior, physiology, and metabolism. In mammalian systems, the suprachiasmatic nucleus (SCN), which is located in the hypothalamus, is the locus of a master circadian clock. The SCN controls the expression of of proteins in a time dependent manner through a genetic feedback loop initiated by light passing through the eye.<ref>doi: 10.1111/ejn.12593</ref> The core molecular clockwork is composed of a transcriptional/post-translational feedback loop: CLOCK:BMAL1 (transcriptional activators) and PER:CRY (transcriptional repressors). In daytime, CLOCK and BMAL1 will form a heterodimer complex and binds to the E-box promoter region of other circadian rhythm proteins, following by the initiation of the transcription of Per (''Period'') and Cry (''Cryptochrome''). During the day, Per and Cry will dimerize and translocate into the nucleus, where they interact with CLOCK:BMAL1 to inhibit their own transcription. This process is called the negative feedback loop.<ref>DOI: 10.1126/science.1222804</ref> At night time, Per:Cry complex is degradated by a specific E3 ligase complex and the repression will be relieved. After the repression level of Per:Cry is decreased, CLOCK:BMAL1 will be re-activated and start a new transcription. This process is called the positive feedback loop. The whole negative/positive feedback loops take around 24 h to complete, thus form the core mechanism of the circadian clock in mammals.<ref>doi:10.1016/B978-0-12-387690-4.00006-4</ref> <br /> <br /> ==The Overall structure of CLOCK:BMAL1 complex==<br /> <br /> The <scene name='60/609802/Clock_bmal1/1'>3D structure of CLOCK:BMAL1 heterodimer</scene> is shown in the right. It is a tightly interwined structure that CLOCK and BMAL1 are twisted together. Although the primary sequences of CLOCK and BMAL1 are similar, the structural arrangements of their domains are quite different.<br /> <br /> ===CLOCK===<br /> <br /> <scene name='60/609802/Clock_only/1'>CLOCK</scene> is composed of three domains: one <scene name='60/609802/Clock_bhlh/1'>N-terminal bHLH</scene> domain, two PAS domains (<scene name='60/609802/Clock_psa_a/1'>PSA-A</scene> and <scene name='60/609802/Clock_psa_b/1'>PSA-B</scene>). The connections between each domain are two <scene name='60/609802/Clock_l1_l2/1'>flexible loops</scene>. Comparing to the flexible loops in BMAL1, the distances of the connection loops in CLOCK are longer.<br /> <br /> ===BMAL1===<br /> <br /> <scene name='60/609802/Bmal1_only/1'>BMAL1</scene> is also composed of three domains: one <scene name='60/609802/Bmal1_bhlh/1'>N-terminal bHLH</scene> domain, two PAS domains (<scene name='60/609802/Bmal1_psa_a/1'>PSA-A</scene> and <scene name='60/609802/Bmal1_psa_b/1'>PSA-B</scene>). There are ~15-residue flexible loop (<scene name='60/609802/Bmal1_l1/1'>L1</scene>) and ~20-residue flexible loop (<scene name='60/609802/Bmal1_l2/1'>L2</scene>) connect between each domains.<br /> <br /> ==The interface between CLOCK and BMAL1==<br /> <br /> In the formation of CLOCK:BMAL1 heterodimer complex, each domain interacts with the corresponding domain of its partner subunit, which means CLOCK bHLH interacts with BMAL1 bHLH domain, CLOCK PSA-A interacts with BMAL1 PSA-A domain, and CLOCK PSA-B interacts with BMAL1 PSA-B domain. In PSA domains, <scene name='60/609802/Clock_bmal1_psa_a/1'>both CLOCK and BMAL1 PSA-A domains</scene> contain five-stranded antiparallel β sheet and several α helices flanking the concave surface of the sheet. In those α helices, there are two <scene name='60/609802/Clock_bmal1_a_alpha/1'>N-terminal flanking helix (A'α) externals</scene> pack in between the β-sheet faces of two domains to mediate the heterodimeric PSA-A interactions. <br /> <br /> === PSA-A domain interface ===<br /> <br /> The interface between CLOCK:BMAL1 PSA-A dimer is mainly facilitated by hydrophobic interactions. Specifically, Phe104, Leu105, and Leu113 on <scene name='60/609802/Clock_bmal1_if_1/1'>the A'α helix of CLOCK contact the hydrophobic region on the β-sheet face of BMAL1</scene> (Leu159, Thr285, Tyr287, Val315, and Ile317). Similarly, Phe141, Leu142, and Leu150 on BMAL1 PSA-A contact to the hydrophobic β-sheet face of CLOCK (F122, I216, V252, and T254). As a result, many residues obtained in the CLOCK:BMAL1 interface are conserved among bHLH-PAS transcription factors. This result may indicate that CLOCK and BMAL1 have a common PSA-A domain dimerization mode.<br /> <br /> ===PSA-B domain interface===<br /> <br /> The PSA-B domains of CLOCK and BMAL1 are stacked in parallel conformation. The β-sheet on PSA-B domain of BMAL1 contacts with the helical face of CLOCK PSA-B domain. The <scene name='60/609802/Clock_bmal1_if_2/1'>contact interface</scene> bury some hydrophobic residues on both subunits, including Try310, Val315, and Leu318 of CLOCK and Phe423, Trp427, and Val435 of BMAL1. <br /> <br /> ===The binding interface between CLOCK:BMAL1 and E-box element===<br /> <br /> <br /> <br /> <br /> == The downstream effects of the altered circadian rhythm ==<br /> <br /> It has been shown in recent years that people who have lifestyles which involve light exposure that is different than the normal 12 hours of daylight/12 hours of night have significantly increased chances of developing cancer. This indicates that disruption of the normal circadian rhythm gene regulation cycle has severe downstream effects on the host's genetic makeup. Additionally, it has been shown that cancer tissues often have distorted circadian rhythms, showing the significance of circadian rhythms to cancer progression. <ref>doi: 10.1097/01.ede.0000152525.21924.54</ref><br /> <br /> Mutated forms of CLOCK exist which do not regulate protein expression correctly and thereby result in altered circadian rhythms. CLOCK-delta19 is a mutant form of CLOCK which binds to BMAL1 normally but the resulting heterodimer does not activate transcription of certain other circadian rhythm proteins. Mutant mice carrying this altered CLOCK protein have shown abnormal circadian rhythms as a result. An example of the downstream effect of this mutant form of CLOCK is the resulting abnormal expression of NAMPT. In normal mice, NAMPT is expressed in a circadian manner, showing oscillations in expression regardless of light conditions. However, in mice with mutant CLOCK-delta19, NAMPT is not expressed in an circadian manner and the overall expression is lower. This leads to further issues as NAMPT is the rate limiting enzyme for the biosynthesis of NAD+, which is an important biological coenzyme.<ref>DOI: 10.1126/science.1171641</ref><br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2071895 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-12-02T23:56:59Z

<p>Joseph Hardie: </p> <hr /> <div>==CLOCK:BMAL1 heterodimer complex==<br /> <br /> <br /> <StructureSection load='4F3L' size='340' side='right' caption='mouse CLOCK:BMAL1 heterodimer complex' scene='60/609802/Clock_bmal1/1'><br /> The <scene name='60/609802/Clock_bmal1/1'>CLOCK:BMAL1 heterodimer complex</scene> is a vital regulatory component of the circadian rhythm protein regulation system. CLOCK (''Circadian Locomotor Output Cycles Kaput'') and BMAL1 (''Brain and muscle Arnt-like protein-1'') are <scene name='60/609802/Bhlh_ex/1'>the basic helix-loop-helix</scene> PER-ARNT-SIM (bHLH-PAS) proteins (The structure highlighted in yellow is just a portion of bHLH structure in CLOCK). They are the main transcriptional activators in the mammalian circadian mechanism.<ref>DOI: 10.1126/science.280.5369.1564</ref> The binding between CLOCK and BMAL1 involves the N-terminal bHLH, PAS-A and PAS-B domains of both proteins. Each domain binds to its corresponding equivalent domain in the other protein. Though both proteins contain the same types of domains with similar primary amino acid sequences in each, the overall heterodimer is surprisingly asymmetrical due to differences in the spatial orientation of the domains in each protein. Since this heterodimer complex involves the binding of all of the major domains in both participating proteins, the overall binding affinity is very high.<br /> <br /> == The role in Circadian Rhythm ==<br /> <br /> Circadian rhythms are operated by an endogenous core clock system that drives daily rhythms in behavior, physiology, and metabolism. In mammalian systems, the suprachiasmatic nucleus (SCN), which is located in the hypothalamus, is the locus of a master circadian clock. The SCN controls the expression of of proteins in a time dependent manner through a genetic feedback loop initiated by light passing through the eye.<ref>doi: 10.1111/ejn.12593</ref> The core molecular clockwork is composed of a transcriptional/post-translational feedback loop: CLOCK:BMAL1 (transcriptional activators) and PER:CRY (transcriptional repressors). In daytime, CLOCK and BMAL1 will form a heterodimer complex and binds to the E-box promoter region of other circadian rhythm proteins, following by the initiation of the transcription of Per (''Period'') and Cry (''Cryptochrome''). During the day, Per and Cry will dimerize and translocate into the nucleus, where they interact with CLOCK:BMAL1 to inhibit their own transcription. This process is called the negative feedback loop.<ref>DOI: 10.1126/science.1222804</ref> At night time, Per:Cry complex is degradated by a specific E3 ligase complex and the repression will be relieved. After the repression level of Per:Cry is decreased, CLOCK:BMAL1 will be re-activated and start a new transcription. This process is called the positive feedback loop. The whole negative/positive feedback loops take around 24 h to complete, thus form the core mechanism of the circadian clock in mammals.<ref>doi:10.1016/B978-0-12-387690-4.00006-4</ref> <br /> <br /> ==The Overall structure of CLOCK:BMAL1 complex==<br /> <br /> The <scene name='60/609802/Clock_bmal1/1'>3D structure of CLOCK:BMAL1 heterodimer</scene> is shown in the right. It is a tightly interwined structure that CLOCK and BMAL1 are twisted together. Although the primary sequences of CLOCK and BMAL1 are similar, the structural arrangements of their domains are quite different.<br /> <br /> ===CLOCK===<br /> <br /> <scene name='60/609802/Clock_only/1'>CLOCK</scene> is composed of three domains: one <scene name='60/609802/Clock_bhlh/1'>N-terminal bHLH</scene> domain, two PAS domains (<scene name='60/609802/Clock_psa_a/1'>PSA-A</scene> and <scene name='60/609802/Clock_psa_b/1'>PSA-B</scene>). The connections between each domain are two <scene name='60/609802/Clock_l1_l2/1'>flexible loops</scene>. Comparing to the flexible loops in BMAL1, the distances of the connection loops in CLOCK are longer.<br /> <br /> ===BMAL1===<br /> <br /> <scene name='60/609802/Bmal1_only/1'>BMAL1</scene> is also composed of three domains: one <scene name='60/609802/Bmal1_bhlh/1'>N-terminal bHLH</scene> domain, two PAS domains (<scene name='60/609802/Bmal1_psa_a/1'>PSA-A</scene> and <scene name='60/609802/Bmal1_psa_b/1'>PSA-B</scene>). There are ~15-residue flexible loop (<scene name='60/609802/Bmal1_l1/1'>L1</scene>) and ~20-residue flexible loop (<scene name='60/609802/Bmal1_l2/1'>L2</scene>) connect between each domains.<br /> <br /> ==The interface between CLOCK and BMAL1==<br /> <br /> In the formation of CLOCK:BMAL1 heterodimer complex, each domain interacts with the corresponding domain of its partner subunit, which means CLOCK bHLH interacts with BMAL1 bHLH domain, CLOCK PSA-A interacts with BMAL1 PSA-A domain, and CLOCK PSA-B interacts with BMAL1 PSA-B domain. In PSA domains, <scene name='60/609802/Clock_bmal1_psa_a/1'>both CLOCK and BMAL1 PSA-A domains</scene> contain five-stranded antiparallel β sheet and several α helices flanking the concave surface of the sheet. In those α helices, there are two <scene name='60/609802/Clock_bmal1_a_alpha/1'>N-terminal flanking helix (A'α) externals</scene> pack in between the β-sheet faces of two domains to mediate the heterodimeric PSA-A interactions. <br /> <br /> === PSA-A domain interface ===<br /> <br /> The interface between CLOCK:BMAL1 PSA-A dimer is mainly facilitated by hydrophobic interactions. Specifically, Phe104, Leu105, and Leu113 on <scene name='60/609802/Clock_bmal1_if_1/1'>the A'α helix of CLOCK contact the hydrophobic region on the β-sheet face of BMAL1</scene> (Leu159, Thr285, Tyr287, Val315, and Ile317). Similarly, Phe141, Leu142, and Leu150 on BMAL1 PSA-A contact to the hydrophobic β-sheet face of CLOCK (F122, I216, V252, and T254). As a result, many residues obtained in the CLOCK:BMAL1 interface are conserved among bHLH-PAS transcription factors. This result may indicate that CLOCK and BMAL1 have a common PSA-A domain dimerization mode.<br /> <br /> ===PSA-B domain interface===<br /> <br /> The PSA-B domains of CLOCK and BMAL1 are stacked in parallel conformation. The β-sheet on PSA-B domain of BMAL1 contacts with the helical face of CLOCK PSA-B domain. The <scene name='60/609802/Clock_bmal1_if_2/1'>contact interface</scene> bury some hydrophobic residues on both subunits, including Try310, Val315, and Leu318 of CLOCK and Phe423, Trp427, and Val435 of BMAL1. <br /> <br /> ===The binding interface between CLOCK:BMAL1 and E-box element===<br /> <br /> <br /> <br /> <br /> == The downstream effects of the altered circadian rhythm ==<br /> <br /> It has been shown in recent years that people who have lifestyles which involve light exposure that is different than the normal 12 hours of daylight/12 hours of night have significantly increased chances of developing cancer. This indicates that disruption of the normal circadian rhythm gene regulation cycle has severe downstream effects on the host's genetic makeup. Additionally, it has been shown that cancer tissues often have distorted circadian rhythms, showing the significance of circadian rhythms to cancer progression. <ref>doi: 10.1097/01.ede.0000152525.21924.54</ref><br /> <br /> Mutated forms of CLOCK exist which do not regulate protein expression correctly and thereby result in altered circadian rhythms. CLOCK-delta19 is a mutant form of CLOCK which binds to BMAL1 normally but the resulting heterodimer does not activate transcription of certain other circadian rhythm proteins. Mutant mice carrying this altered CLOCK protein have shown abnormal circadian rhythms as a result. An example of the downstream effect of this mutant form of CLOCK is the resulting abnormal expression of NAMPT. In normal mice, NAMPT is expressed in a circadian manner, showing oscillations in expression regardless of light conditions. However, in mice with mutant CLOCK-delta19, NAMPT is not expressed in an circadian manner and the overall expression is lower. This leads to further issues as NAMPT is the rate limiting enzyme for the biosynthesis of NAD+, which is an important biological coenzyme.<ref>DOI: 10.1126/science.1171641</ref><br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2071761 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-12-02T04:13:42Z

<p>Joseph Hardie: </p> <hr /> <div>==CLOCK:BMAL1 heterodimer complex==<br /> <br /> <br /> <StructureSection load='4F3L' size='340' side='right' caption='mouse CLOCK:BMAL1 heterodimer complex' scene=''><br /> The <scene name='60/609802/Clock_bmal1/1'>CLOCK:BMAL1 heterodimer complex</scene> is a vital regulatory component of the circadian rhythm protein regulation system.The binding between CLOCK and BMAL1 involves the N-terminal bHLH, PAS-A and PAS-B domains of both proteins. Each domain binds to its corresponding equivalent domain in the other protein. Though both proteins contain the same types of domains with similar primary amino acid sequences in each, the overall heterodimer is surprisingly asymmetrical due to differences in the spatial orientation of the domains in each protein. Since this heterodimer complex involves the binding of all of the major domains in both participating proteins, the overall binding affinity is very high.<br /> <br /> ==CLOCK==<br /> <br /> <scene name='60/609802/Clock_only/1'>CLOCK</scene> is a protein central to the regulation of the mammalian circadian rhythm system. CLOCK is a helix-loop-helix-PER-ARNT-SIM (bHLH-PAS) protein that regulates the circadian rhythm by forming heterodimers with other circadian rhythm proteins to activate the transcription of other proteins.<ref>DOI:10.1126/science.280.5369.1564</ref> <scene name='60/609802/Clock_helix_sheets/1'>The structure of CLOCK</scene> consists of 12 alpha-helixes and 8 beta-sheets. In between the helixes and sheets, there are many flexible loops, which are the main contributions to the CLOCK:BMAL1 interactions.<br /> <br /> ==BMAL1==<br /> <scene name='60/609802/Bmal1_only/1'>BMAL1</scene><br /> <br /> == Circadian Rhythm ==<br /> <br /> The circadian rhythm is the 24 hour protein regulation system found in most mammalian species. The circadian rhythm causes certain proteins to be expressed during the day and then downregulated during the night. The circadian rhythm originates in the suprachiasmatic nucleus (SCN), which is located in the hypothalamus. The SCN controls the expression of of proteins in a time dependent manner through a genetic feedback loop initiated by light passing through the eye. The CLOCK:BMAL1 heterodimer complex is a vital component of this system as this heterodimer binds to the E-box promoter region of other circadian rhythm proteins and trigger the transcription of those proteins. These proteins then repress their own transcription in order to regulate the protein content to the appropriate levels.<br /> <ref>DOI: 10.1126/science.1222804</ref><br /> <br /> == Disease ==<br /> <br /> Mutated forms of CLOCK exist which do not regulate protein expression correctly and thereby result in altered circadian rhythms. CLOCK-delta19 is a mutant form of CLOCK which binds to BMAL1 normally but the resulting heterodimer does not activate transcription of certain other circadian rhythm proteins. Mutant mice carrying this altered CLOCK protein have shown abnormal circadian rhythms as a result. <ref>DOI: 10.1126/science.1171641</ref><br /> <br /> It has been shown in recent years that people who have lifestyles which involve light exposure that is different than the normal 12 hours of daylight/12 hours of night have significantly increased chances of developing cancer. This indicates that disruption of the normal circadian rhythm gene regulation cycle has severe downstream effects on the host's genetic makeup. Additionally, it has been shown that cancer tissues often have distorted circadian rhythms, showing the significance of circadian rhythms to cancer progression. <ref>doi: 10.1097/01.ede.0000152525.21924.54</ref><br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2071751 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-12-01T21:55:07Z

<p>Joseph Hardie: </p> <hr /> <div>==CLOCK:BMAL1 heterodimer complex==<br /> <br /> <br /> <StructureSection load='4F3L' size='340' side='right' caption='mouse CLOCK:BMAL1 heterodimer complex' scene=''><br /> The <scene name='60/609802/Clockbmal1/1'>CLOCK:BMAL1 heterodimer complex</scene> is a vital regulatory component of the circadian rhythm protein regulation system.<br /> <br /> <br /> ==CLOCK==<br /> <br /> <scene name='60/609802/Clock/5'>CLOCK</scene> is a protein central to the regulation of the mammalian circadian rhythm system. CLOCK is a helix-loop-helix-PER-ARNT-SIM (bHLH-PAS) protein that regulates the circadian rhythm by forming heterodimers with other circadian rhythm proteins to activate the transcription of other proteins. <br /> <ref>DOI:10.1126/science.280.5369.1564</ref><br /> <br /> ==BMAL1==<br /> <br /> ==Heterodimer complex==<br /> The binding between CLOCK and BMAL1 involves the N-terminal bHLH, PAS-A and PAS-B domains of both proteins. Each domain binds to its corresponding equivalent domain in the other protein. Though both proteins contain the same types of domains with similar primary amino acid sequences in each, the overall heterodimer is surprisingly asymmetrical due to differences in the spatial orientation of the domains in each protein. Since this heterodimer complex involves the binding of all of the major domains in both participating proteins, the overall binding affinity is very high.<br /> <ref>DOI: 10.1126/science.1222804</ref><br /> <br /> == Circadian Rhythm ==<br /> <br /> The circadian rhythm is the 24 hour protein regulation system found in most mammalian species. The circadian rhythm causes certain proteins to be expressed during the day and then downregulated during the night. The circadian rhythm originates in the suprachiasmatic nucleus (SCN), which is located in the hypothalamus. The SCN controls the expression of of proteins in a time dependent manner through a genetic feedback loop initiated by light passing through the eye. The CLOCK:BMAL1 heterodimer complex is a vital component of this system as this heterodimer binds to the E-box promoter region of other circadian rhythm proteins and trigger the transcription of those proteins. These proteins then repress their own transcription in order to regulate the protein content to the appropriate levels.<br /> <ref>doi:10.1016/j.cmet.2006.07.002</ref><br /> == Disease ==<br /> <br /> Mutated forms of CLOCK exist which do not regulate protein expression correctly and thereby result in altered circadian rhythms. CLOCK-delta19 is a mutant form of CLOCK which binds to BMAL1 normally but the resulting heterodimer does not activate transcription of certain other circadian rhythm proteins. Mutant mice carrying this altered CLOCK protein have shown abnormal circadian rhythms as a result. <ref>DOI: 10.1126/science.1171641</ref><br /> <br /> It has been shown in recent years that people who have lifestyles which involve light exposure that is different than the normal 12 hours of daylight/12 hours of night have significantly increased chances of developing cancer. This indicates that disruption of the normal circadian rhythm gene regulation cycle has severe downstream effects on the host's genetic makeup. Additionally, it has been shown that cancer tissues often have distorted circadian rhythms, showing the significance of circadian rhythms to cancer progression. <ref>doi: 10.1097/01.ede.0000152525.21924.54</ref><br /> <br /> <br /> == Structural highlights ==<br /> <br /> <scene name='60/609802/Clock-2/1'>CLOCK</scene> and <scene name='60/609802/Bmal1/2'>BMAL1</scene> will form a heterodimer complex.<br /> <br /> <br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2071674 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-12-01T16:56:26Z

<p>Joseph Hardie: </p> <hr /> <div>==CLOCK:BMAL1 heterodimer complex==<br /> <br /> <br /> <StructureSection load='4F3L' size='340' side='right' caption='CLOCK:BMAL1 heterodimer complex' scene=''><br /> The <scene name='60/609802/Clockbmal1/1'>CLOCK:BMAL1 heterodimer complex</scene> is a vital regulatory component of the circadian rhythm protein regulation system.<br /> <br /> <br /> ==CLOCK==<br /> <br /> <scene name='60/609802/Clock/5'>CLOCK</scene> is a protein central to the regulation of the mammalian circadian rhythm system. CLOCK is a helix-loop-helix-PER-ARNT-SIM (bHLH-PAS) protein that regulates the circadian rhythm by forming heterodimers with other circadian rhythm proteins to activate the transcription of other proteins. <br /> <ref>DOI:10.1126/science.280.5369.1564</ref><br /> <br /> ==BMAL1==<br /> <br /> ==Heterodimer complex==<br /> The binding between CLOCK and BMAL1 involves the N-terminal bHLH, PAS-A and PAS-B domains of both proteins. Each domain binds to its corresponding equivalent domain in the other protein. Though both proteins contain the same types of domains with similar primary amino acid sequences in each, the overall heterodimer is surprisingly asymmetrical due to differences in the spatial orientation of the domains in each protein. Since this heterodimer complex involves the binding of all of the major domains in both participating proteins, the overall binding affinity is very high.<br /> <br /> == Circadian Rhythm ==<br /> <br /> The circadian rhythm is the 24 hour protein regulation system found in most mammalian species. The circadian rhythm causes certain proteins to be expressed during the day and then downregulated during the night. The circadian rhythm originates in the suprachiasmatic nucleus (SCN), which is located in the hypothalamus. The SCN controls the expression of of proteins in a time dependent manner through a genetic feedback loop initiated by light passing through the eye. The CLOCK:BMAL1 heterodimer complex is a vital component of this system as this heterodimer binds to the E-box promoter region of other circadian rhythm proteins and trigger the transcription of those proteins. These proteins then repress their own transcription in order to regulate the protein content to the appropriate levels.<br /> <ref>DOI: 10.1126/science.1222804</ref><br /> == Disease ==<br /> <br /> Mutated forms of CLOCK exist which do not regulate protein expression correctly and thereby result in altered circadian rhythms. CLOCK-delta19 is a mutant form of CLOCK which binds to BMAL1 normally but the resulting heterodimer does not activate transcription of certain other circadian rhythm proteins. Mutant mice carrying this altered CLOCK protein have shown abnormal circadian rhythms as a result. <ref>DOI: 10.1126/science.1171641</ref><br /> <br /> It has been shown in recent years that people who have lifestyles which involve light exposure that is different than the normal 12 hours of daylight/12 hours of night have significantly increased chances of developing cancer. This indicates that disruption of the normal circadian rhythm gene regulation cycle has severe downstream effects on the host's genetic makeup. Additionally, it has been shown that cancer tissues often have distorted circadian rhythms, showing the significance of circadian rhythms to cancer progression. <ref>doi: 10.1097/01.ede.0000152525.21924.54</ref><br /> <br /> <br /> == Structural highlights ==<br /> <br /> <scene name='60/609802/Clock-2/1'>CLOCK</scene> and <scene name='60/609802/Bmal1/2'>BMAL1</scene> will form a heterodimer complex.<br /> <br /> <br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2071672 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-12-01T16:51:14Z

<p>Joseph Hardie: </p> <hr /> <div>==CLOCK:BMAL1 heterodimer complex==<br /> <br /> <br /> <StructureSection load='4F3L' size='340' side='right' caption='CLOCK:BMAL1 heterodimer complex' scene=''><br /> The <scene name='60/609802/Clockbmal1/1'>CLOCK:BMAL1 heterodimer complex</scene> is a vital regulatory component of the circadian rhythm protein regulation system.<br /> <br /> <br /> ==CLOCK==<br /> <br /> <scene name='60/609802/Clock/5'>CLOCK</scene> is a protein central to the regulation of the mammalian circadian rhythm system. CLOCK is a helix-loop-helix-PER-ARNT-SIM (bHLH-PAS) protein that regulates the circadian rhythm by forming heterodimers with other circadian rhythm proteins to activate the transcription of other proteins. <br /> <ref>DOI:10.1126/science.280.5369.1564</ref><br /> <br /> ==BMAL1==<br /> <br /> ==Heterodimer complex==<br /> The binding between CLOCK and BMAL1 involves the N-terminal bHLH, PAS-A and PAS-B domains of both proteins. Each domain binds to its corresponding equivalent domain in the other protein. Though both proteins contain the same types of domains with similar primary amino acid sequences in each, the overall heterodimer is surprisingly asymmetrical due to differences in the spatial orientation of the domains in each protein. Since this heterodimer complex involves the binding of all of the major domains in both participating proteins, the overall binding affinity is very high.<br /> <br /> == Circadian Rhythm ==<br /> <br /> The circadian rhythm is the 24 hour protein regulation system found in most mammalian species. The circadian rhythm causes certain proteins to be expressed during the day and then downregulated during the night. The circadian rhythm originates in the suprachiasmatic nucleus (SCN), which is located in the hypothalamus. The SCN controls the expression of of proteins in a time dependent manner through a genetic feedback loop initiated by light passing through the eye. The CLOCK:BMAL1 heterodimer complex is a vital component of this system as this heterodimer binds to the E-box promoter region of other circadian rhythm proteins and trigger the transcription of those proteins. These proteins then repress their own transcription in order to regulate the protein content to the appropriate levels.<br /> <ref>DOI: 10.1126/science.1222804</ref><br /> == Disease ==<br /> <br /> Mutated forms of CLOCK exist which do not regulate protein expression correctly and thereby result in altered circadian rhythms. CLOCK-delta19 is a mutant form of CLOCK which binds to BMAL1 normally but the resulting heterodimer does not activate transcription of certain other circadian rhythm proteins. Mutant mice carrying this altered CLOCK protein have shown abnormal circadian rhythms as a result.<br /> <br /> It has been shown in recent years that people who have lifestyles which involve light exposure that is different than the normal 12 hours of daylight/12 hours of night have significantly increased chances of developing cancer. This indicates that disruption of the normal circadian rhythm gene regulation cycle has severe downstream effects on the host's genetic makeup. Additionally, it has been shown that cancer tissues often have distorted circadian rhythms, showing the significance of circadian rhythms to cancer progression. <ref>doi: 10.1097/01.ede.0000152525.21924.54</ref><br /> <br /> <br /> == Structural highlights ==<br /> <br /> <scene name='60/609802/Clock-2/1'>CLOCK</scene> and <scene name='60/609802/Bmal1/2'>BMAL1</scene> will form a heterodimer complex.<br /> <br /> <br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2071671 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-12-01T16:48:48Z

<p>Joseph Hardie: </p> <hr /> <div>==CLOCK:BMAL1 heterodimer complex==<br /> <br /> <br /> <StructureSection load='4F3L' size='340' side='right' caption='CLOCK:BMAL1 heterodimer complex' scene=''><br /> The <scene name='60/609802/Clockbmal1/1'>CLOCK:BMAL1 heterodimer complex</scene> is a vital regulatory component of the circadian rhythm protein regulation system.<br /> <br /> <br /> ==CLOCK==<br /> <br /> <scene name='60/609802/Clock/5'>CLOCK</scene> is a protein central to the regulation of the mammalian circadian rhythm system. CLOCK is a helix-loop-helix-PER-ARNT-SIM (bHLH-PAS) protein that regulates the circadian rhythm by forming heterodimers with other circadian rhythm proteins to activate the transcription of other proteins. <br /> <ref>DOI:10.1126/science.280.5369.1564</ref><br /> <br /> ==BMAL1==<br /> <br /> ==Heterodimer complex==<br /> The binding between CLOCK and BMAL1 involves the N-terminal bHLH, PAS-A and PAS-B domains of both proteins. Each domain binds to its corresponding equivalent domain in the other protein. Though both proteins contain the same types of domains with similar primary amino acid sequences in each, the overall heterodimer is surprisingly asymmetrical due to differences in the spatial orientation of the domains in each protein. Since this heterodimer complex involves the binding of all of the major domains in both participating proteins, the overall binding affinity is very high.<br /> <br /> == Circadian Rhythm ==<br /> <br /> The circadian rhythm is the 24 hour protein regulation system found in most mammalian species. The circadian rhythm causes certain proteins to be expressed during the day and then downregulated during the night. The circadian rhythm originates in the suprachiasmatic nucleus (SCN), which is located in the hypothalamus. The SCN controls the expression of of proteins in a time dependent manner through a genetic feedback loop initiated by light passing through the eye. The CLOCK:BMAL1 heterodimer complex is a vital component of this system as this heterodimer binds to the E-box promoter region of other circadian rhythm proteins and trigger the transcription of those proteins. These proteins then repress their own transcription in order to regulate the protein content to the appropriate levels.<br /> <ref>DOI: 10.1126/science.1222804</ref><br /> == Disease ==<br /> <br /> Mutated forms of CLOCK exist which do not regulate protein expression correctly and thereby result in altered circadian rhythms. CLOCK-delta19 is a mutant form of CLOCK which binds to BMAL1 normally but the resulting heterodimer does not activate transcription of certain other circadian rhythm proteins. Mutant mice carrying this altered CLOCK protein have shown abnormal circadian rhythms as a result.<br /> <br /> It has been shown in recent years that people who have lifestyles which involve light exposure that is different than the normal 12 hours of daylight/12 hours of night have significantly increased chances of developing cancer. This indicates that disruption of the normal circadian rhythm gene regulation cycle has severe downstream effects on the host's genetic makeup. Additionally, it has been shown that cancer tissues often have distorted circadian rhythms, showing the significance of circadian rhythms to cancer progression. <ref>doi: 10.1097/01.ede.0000152525.21924.54</ref><br /> <br /> == Relevance ==<br /> <br /> == Structural highlights ==<br /> <br /> <scene name='60/609802/Clock-2/1'>CLOCK</scene> and <scene name='60/609802/Bmal1/2'>BMAL1</scene> will form a heterodimer complex.<br /> <br /> <br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2071664 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-12-01T16:44:15Z

<p>Joseph Hardie: </p> <hr /> <div>==CLOCK:BMAL1 heterodimer complex==<br /> <br /> <br /> <StructureSection load='4F3L' size='340' side='right' caption='CLOCK:BMAL1 heterodimer complex' scene=''><br /> The <scene name='60/609802/Clockbmal1/1'>CLOCK:Bmal1 heterodimer complex</scene> is a vital regulatory component of the circadian rhythm protein regulation system.<br /> <br /> <br /> ==CLOCK==<br /> <br /> <scene name='60/609802/Clock/5'>CLOCK</scene> is a protein central to the regulation of the mammalian circadian rhythm system. CLOCK is a helix-loop-helix-PER-ARNT-SIM (bHLH-PAS) protein that regulates the circadian rhythm by forming heterodimers with other circadian rhythm proteins to activate the transcription of other proteins. <br /> <ref>DOI:10.1126/science.280.5369.1564</ref><br /> <br /> ==BMAL1==<br /> <br /> ==Heterodimer complex==<br /> The binding between CLOCK and BMAL1 involves the N-terminal bHLH, PAS-A and PAS-B domains of both proteins. Each domain binds to its corresponding equivalent domain in the other protein. Though both proteins contain the same types of domains with similar primary amino acid sequences in each, the overall heterodimer is surprisingly asymmetrical due to differences in the spatial orientation of the domains in each protein. Since this heterodimer complex involves the binding of all of the major domains in both participating proteins, the overall binding affinity is very high.<br /> <br /> == Circadian Rhythm ==<br /> <br /> The circadian rhythm is the 24 hour protein regulation system found in most mammalian species. The circadian rhythm causes certain proteins to be expressed during the day and then downregulated during the night. The circadian rhythm originates in the suprachiasmatic nucleus (SCN), which is located in the hypothalamus. The SCN controls the expression of of proteins in a time dependent manner through a genetic feedback loop initiated by light passing through the eye. The CLOCK:BMAL1 heterodimer complex is a vital component of this system as this heterodimer binds to the E-box promoter region of other circadian rhythm proteins and trigger the transcription of those proteins. These proteins then repress their own transcription in order to regulate the protein content to the appropriate levels.<br /> <ref>DOI: 10.1126/science.1222804</ref><br /> == Disease ==<br /> <br /> Mutated forms of CLOCK exist which do not regulate protein expression correctly and thereby result in altered circadian rhythms. CLOCK-delta19 is a mutant form of CLOCK which binds to BMAL1 normally but the resulting heterodimer does not activate transcription of certain other circadian rhythm proteins. Mutant mice carrying this altered CLOCK protein have shown abnormal circadian rhythms as a result.<br /> <br /> It has been shown in recent years that people who have lifestyles which involve light exposure that is different than the normal 12 hours of daylight/12 hours of night have significantly increased chances of developing cancer. This indicates that disruption of the normal circadian rhythm gene regulation cycle has severe downstream effects on the host's genetic makeup. Additionally, it has been shown that cancer tissues often have distorted circadian rhythms, showing the significance of circadian rhythms to cancer progression. <ref>doi: 10.1097/01.ede.0000152525.21924.54</ref><br /> <br /> == Relevance ==<br /> <br /> == Structural highlights ==<br /> <br /> <scene name='60/609802/Clock-2/1'>CLOCK</scene> and <scene name='60/609802/Bmal1/2'>BMAL1</scene> will form a heterodimer complex.<br /> <br /> <br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2071661 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-12-01T16:40:48Z

<p>Joseph Hardie: </p> <hr /> <div>==CLOCK:BMAL1 heterodimer complex==<br /> <br /> <br /> <StructureSection load='4F3L' size='340' side='right' caption='CLOCK:BMAL1 heterodimer complex' scene=''><br /> The <scene name='60/609802/Clockbmal1/1'>CLOCK:Bmal1 heterodimer complex</scene> is a vital regulatory component of the circadian rhythm protein regulation system.<br /> <br /> <br /> ==CLOCK==<br /> <br /> <scene name='60/609802/Clock/5'>CLOCK</scene> is a protein central to the regulation of the mammalian circadian rhythm system. CLOCK is a helix-loop-helix-PER-ARNT-SIM (bHLH-PAS) protein that regulates the circadian rhythm by forming heterodimers with other circadian rhythm proteins to activate the transcription of other proteins. <br /> <ref>DOI:10.1126/science.280.5369.1564</ref><br /> <br /> ==BMAL1==<br /> <br /> ==Heterodimer complex==<br /> The binding between CLOCK and BMAL1 involves the N-terminal bHLH, PAS-A and PAS-B domains of both proteins. Each domain binds to its corresponding equivalent domain in the other protein. Though both proteins contain the same types of domains with similar primary amino acid sequences in each, the overall heterodimer is surprisingly asymmetrical due to differences in the spatial orientation of the domains in each protein. <br /> <br /> == Circadian Rhythm ==<br /> <br /> The circadian rhythm is the 24 hour protein regulation system found in most mammalian species. The circadian rhythm causes certain proteins to be expressed during the day and then downregulated during the night. The circadian rhythm originates in the suprachiasmatic nucleus (SCN), which is located in the hypothalamus. The SCN controls the expression of of proteins in a time dependent manner through a genetic feedback loop initiated by light passing through the eye. The CLOCK:BMAL1 heterodimer complex is a vital component of this system as this heterodimer binds to the E-box promoter region of other circadian rhythm proteins and trigger the transcription of those proteins. These proteins then repress their own transcription in order to regulate the protein content to the appropriate levels.<br /> <ref>DOI: 10.1126/science.1222804</ref><br /> == Disease ==<br /> <br /> Mutated forms of CLOCK exist which do not regulate protein expression correctly and thereby result in altered circadian rhythms. CLOCK-delta19 is a mutant form of CLOCK which binds to BMAL1 normally but the resulting heterodimer does not activate transcription of certain other circadian rhythm proteins. Mutant mice carrying this altered CLOCK protein have shown abnormal circadian rhythms as a result.<br /> <br /> It has been shown in recent years that people who have lifestyles which involve light exposure that is different than the normal 12 hours of daylight/12 hours of night have significantly increased chances of developing cancer. This indicates that disruption of the normal circadian rhythm gene regulation cycle has severe downstream effects on the host's genetic makeup. Additionally, it has been shown that cancer tissues often have distorted circadian rhythms, showing the significance of circadian rhythms to cancer progression. <ref>doi: 10.1097/01.ede.0000152525.21924.54</ref><br /> <br /> == Relevance ==<br /> <br /> == Structural highlights ==<br /> <br /> <scene name='60/609802/Clock-2/1'>CLOCK</scene> and <scene name='60/609802/Bmal1/2'>BMAL1</scene> will form a heterodimer complex.<br /> <br /> <br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2071659 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-12-01T16:38:21Z

<p>Joseph Hardie: </p> <hr /> <div>==CLOCK:BMAL1 heterodimer complex==<br /> <br /> <br /> <StructureSection load='4F3L' size='340' side='right' caption='CLOCK:BMAL1 heterodimer complex' scene=''><br /> The <scene name='60/609802/Clockbmal1/1'>CLOCK:Bmal1 heterodimer complex</scene> is a vital regulatory component of the circadian rhythm protein regulation system.<br /> <br /> <br /> ==CLOCK==<br /> <br /> <scene name='60/609802/Clock/5'>CLOCK</scene> is a protein central to the regulation of the mammalian circadian rhythm system. CLOCK is a helix-loop-helix-PER-ARNT-SIM (bHLH-PAS) protein that regulates the circadian rhythm by forming heterodimers with other circadian rhythm proteins to activate the transcription of other proteins. <br /> <ref>DOI:10.1126/science.280.5369.1564</ref><br /> <br /> ==BMAL1==<br /> <br /> ==Heterodimer complex==<br /> The binding between CLOCK and BMAL1 involves the N-terminal bHLH, PAS-A and PAS-B domains of both proteins. Each domain binds to its corresponding equivalent domain in the other protein. Though both proteins contain the same types of domains with similar primary amino acid sequences in each, the overall heterodimer is surprisingly asymmetrical. <br /> <br /> == Circadian Rhythm ==<br /> <br /> The circadian rhythm is the 24 hour protein regulation system found in most mammalian species. The circadian rhythm causes certain proteins to be expressed during the day and then downregulated during the night. The circadian rhythm originates in the suprachiasmatic nucleus (SCN), which is located in the hypothalamus. The SCN controls the expression of of proteins in a time dependent manner through a genetic feedback loop initiated by light passing through the eye. The CLOCK:BMAL1 heterodimer complex is a vital component of this system as this heterodimer binds to the E-box promoter region of other circadian rhythm proteins and trigger the transcription of those proteins. These proteins then repress their own transcription in order to regulate the protein content to the appropriate levels.<br /> <ref>DOI: 10.1126/science.1222804</ref><br /> == Disease ==<br /> <br /> Mutated forms of CLOCK exist which do not regulate protein expression correctly and thereby result in altered circadian rhythms. CLOCK-delta19 is a mutant form of CLOCK which binds to BMAL1 normally but the resulting heterodimer does not activate transcription of certain other circadian rhythm proteins. Mutant mice carrying this altered CLOCK protein have shown abnormal circadian rhythms as a result.<br /> <br /> It has been shown in recent years that people who have lifestyles which involve light exposure that is different than the normal 12 hours of daylight/12 hours of night have significantly increased chances of developing cancer. This indicates that disruption of the normal circadian rhythm gene regulation cycle has severe downstream effects on the host's genetic makeup. Additionally, it has been shown that cancer tissues often have distorted circadian rhythms, showing the significance of circadian rhythms to cancer progression. <ref>doi: 10.1097/01.ede.0000152525.21924.54</ref><br /> <br /> == Relevance ==<br /> <br /> == Structural highlights ==<br /> <br /> <scene name='60/609802/Clock-2/1'>CLOCK</scene> and <scene name='60/609802/Bmal1/2'>BMAL1</scene> will form a heterodimer complex.<br /> <br /> <br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2071654 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-12-01T16:27:50Z

<p>Joseph Hardie: </p> <hr /> <div>==CLOCK:BMAL1 heterodimer complex==<br /> <br /> <br /> <StructureSection load='4F3L' size='340' side='right' caption='CLOCK:BMAL1 heterodimer complex' scene=''><br /> The <scene name='60/609802/Clockbmal1/1'>CLOCK:Bmal1 heterodimer complex</scene> is a vital regulatory component of the circadian rhythm protein regulation system.<br /> <br /> <br /> ==CLOCK==<br /> <br /> <scene name='60/609802/Clock/5'>CLOCK</scene> is a protein central to the regulation of the mammalian circadian rhythm system. CLOCK is a helix-loop-helix-PER-ARNT-SIM (bHLH-PAS) protein that regulates the circadian rhythm by forming heterodimers with other circadian rhythm proteins to activate the transcription of other proteins. <br /> <ref>DOI:10.1126/science.280.5369.1564</ref><br /> <br /> ==BMAL1==<br /> <br /> ==Heterodimer complex==<br /> <br /> == Circadian Rhythm ==<br /> <br /> The circadian rhythm is the 24 hour protein regulation system found in most mammalian species. The circadian rhythm causes certain proteins to be expressed during the day and then downregulated during the night. The circadian rhythm originates in the suprachiasmatic nucleus (SCN), which is located in the hypothalamus. The SCN controls the expression of of proteins in a time dependent manner through a genetic feedback loop initiated by light passing through the eye. The CLOCK:BMAL1 heterodimer complex is a vital component of this system as this heterodimer binds to the E-box promoter region of other circadian rhythm proteins and trigger the transcription of those proteins. These proteins then repress their own transcription in order to regulate the protein content to the appropriate levels.<br /> <ref>DOI: 10.1126/science.1222804</ref><br /> == Disease ==<br /> <br /> Mutated forms of CLOCK exist which do not regulate protein expression correctly and thereby result in altered circadian rhythms. CLOCK-delta19 is a mutant form of CLOCK which binds to BMAL1 normally but the resulting heterodimer does not activate transcription of certain other circadian rhythm proteins. Mutant mice carrying this altered CLOCK protein have shown abnormal circadian rhythms as a result.<br /> <br /> It has been shown in recent years that people who have lifestyles which involve light exposure that is different than the normal 12 hours of daylight/12 hours of night have significantly increased chances of developing cancer. This indicates that disruption of the normal circadian rhythm gene regulation cycle has severe downstream effects on the host's genetic makeup. Additionally, it has been shown that cancer tissues often have distorted circadian rhythms, showing the significance of circadian rhythms to cancer progression. <ref>doi: 10.1097/01.ede.0000152525.21924.54</ref><br /> <br /> == Relevance ==<br /> <br /> == Structural highlights ==<br /> <br /> <scene name='60/609802/Clock-2/1'>CLOCK</scene> and <scene name='60/609802/Bmal1/2'>BMAL1</scene> will form a heterodimer complex.<br /> <br /> <br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2071653 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-12-01T16:22:56Z

<p>Joseph Hardie: </p> <hr /> <div>==CLOCK:BMAL1 heterodimer complex==<br /> <br /> <br /> <StructureSection load='4F3L' size='340' side='right' caption='CLOCK:BMAL1 heterodimer complex' scene=''><br /> The <scene name='60/609802/Clockbmal1/1'>CLOCK:Bmal1 heterodimer complex</scene> is a vital regulatory component of the circadian rhythm protein regulation system.<br /> <br /> <br /> ==CLOCK==<br /> <br /> <scene name='60/609802/Clock/5'>CLOCK</scene> is a protein central to the regulation of the mammalian circadian rhythm system. CLOCK is a helix-loop-helix-PER-ARNT-SIM (bHLH-PAS) protein that regulates the circadian rhythm by forming heterodimers with other circadian rhythm proteins to activate the transcription of other proteins. <br /> <ref>DOI:10.1126/science.280.5369.1564</ref><br /> <br /> ==BMAL1==<br /> <br /> ==Heterodimer complex==<br /> <br /> == Circadian Rhythm ==<br /> <br /> The circadian rhythm is the 24 hour protein regulation system found in most mammalian species. The circadian rhythm causes certain proteins to be expressed during the day and then downregulated during the night. The circadian rhythm originates in the suprachiasmatic nucleus (SCN), which is located in the hypothalamus. The SCN controls the expression of of proteins in a time dependent manner through a genetic feedback loop initiated by light passing through the eye. The CLOCK:BMAL1 heterodimer complex is a vital component of this system as this heterodimer binds to the E-box promoter region of other circadian rhythm proteins and trigger the transcription of those proteins. These proteins then repress their own transcription in order to regulate the protein content to the appropriate levels.<br /> <ref>DOI: 10.1126/science.1222804</ref><br /> == Disease ==<br /> <br /> Mutated forms of CLOCK exist which do not regulate protein expression correctly and thereby result in altered circadian rhythms. CLOCK-delta19 is a mutant form of CLOCK which binds to BMAL1 normally but the resulting heterodimer does not activate transcription of certain other circadian rhythm proteins. Mutant mice carrying this altered CLOCK protein have shown abnormal circadian rhythms as a result.<br /> <br /> It has been shown in recent years that people who have lifestyles which involve light exposure that is different than the normal 12 hours of daylight/12 hours of night have significantly increased chances of developing cancer. This indicates that disruption of the normal circadian rhythm gene regulation cycle has severe downstream effects on the host's genetic makeup. Additionally, it has been shown that cancer tissues often have distorted circadian rhythms, showing the significance of circadian rhythms to cancer progression. <ref>DOI:10.1002/(SICI)1097-0215(19970117)70:2<241::AID-IJC16>3.0.CO;2-L</ref><br /> <br /> == Relevance ==<br /> <br /> == Structural highlights ==<br /> <br /> <scene name='60/609802/Clock-2/1'>CLOCK</scene> and <scene name='60/609802/Bmal1/2'>BMAL1</scene> will form a heterodimer complex.<br /> <br /> <br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2071648 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-12-01T16:14:17Z

<p>Joseph Hardie: </p> <hr /> <div>==CLOCK:BMAL1 heterodimer complex==<br /> <br /> <br /> <StructureSection load='4F3L' size='340' side='right' caption='CLOCK:BMAL1 heterodimer complex' scene=''><br /> The <scene name='60/609802/Clockbmal1/1'>CLOCK:Bmal1 heterodimer complex</scene> is a vital regulatory component of the circadian rhythm protein regulation system.<br /> <br /> <br /> ==CLOCK==<br /> <br /> <scene name='60/609802/Clock/5'>CLOCK</scene> is a protein central to the regulation of the mammalian circadian rhythm system. CLOCK is a helix-loop-helix-PER-ARNT-SIM (bHLH-PAS) protein that regulates the circadian rhythm by forming heterodimers with other circadian rhythm proteins to activate the transcription of other proteins. <br /> <ref>DOI:10.1126/science.280.5369.1564</ref><br /> <br /> ==BMAL1==<br /> <br /> ==Heterodimer complex==<br /> <br /> == Circadian Rhythm ==<br /> <br /> The circadian rhythm is the 24 hour protein regulation system found in most mammalian species. The circadian rhythm causes certain proteins to be expressed during the day and then downregulated during the night. The circadian rhythm originates in the suprachiasmatic nucleus (SCN), which is located in the hypothalamus. The SCN controls the expression of of proteins in a time dependent manner through a genetic feedback loop initiated by light passing through the eye. The CLOCK:BMAL1 heterodimer complex is a vital component of this system as this heterodimer binds to the E-box promoter region of other circadian rhythm proteins and trigger the transcription of those proteins. These proteins then repress their own transcription in order to regulate the protein content to the appropriate levels.<br /> <ref>DOI: 10.1126/science.1222804</ref><br /> == Disease ==<br /> <br /> Mutated forms of CLOCK exist which do not regulate protein expression correctly and thereby result in altered circadian rhythms. CLOCK-delta19 is a mutant form of CLOCK which binds to BMAL1 normally but the resulting heterodimer does not activate transcription of certain other circadian rhythm proteins. Mutant mice carrying this altered CLOCK protein have shown abnormal circadian rhythms as a result.<br /> <br /> It has been shown in recent years that people who have lifestyles which involve light exposure that is different than the normal 12 hours of daylight/12 hours of night have significantly increased chances of developing cancer. This indicates that disruption of the normal circadian rhythm gene regulation cycle has severe downstream effects on the host's genetic makeup.<br /> <br /> == Relevance ==<br /> <br /> == Structural highlights ==<br /> <br /> <scene name='60/609802/Clock-2/1'>CLOCK</scene> and <scene name='60/609802/Bmal1/2'>BMAL1</scene> will form a heterodimer complex.<br /> <br /> <br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2071646 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-12-01T16:10:03Z

<p>Joseph Hardie: </p> <hr /> <div>==CLOCK:BMAL1 heterodimer complex==<br /> <br /> <br /> <StructureSection load='4F3L' size='340' side='right' caption='CLOCK:BMAL1 heterodimer complex' scene=''><br /> The <scene name='60/609802/Clockbmal1/1'>CLOCK:Bmal1 heterodimer complex</scene> is a vital regulatory component of the circadian rhythm protein regulation system.<br /> This is a default text for your page '''Molecular Playground/CLOCK:BMAL1 heterodimer complex'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br /> You may include any references to papers as in: the use of JSmol in Proteopedia or to the article describing Jmol to the rescue.<br /> <br /> ==CLOCK==<br /> <br /> <scene name='60/609802/Clock/5'>CLOCK</scene> is a protein central to the regulation of the mammalian circadian rhythm system. CLOCK is a helix-loop-helix-PER-ARNT-SIM (bHLH-PAS) protein that regulates the circadian rhythm by forming heterodimers with other circadian rhythm proteins to activate the transcription of other proteins. <br /> <ref>DOI:10.1126/science.280.5369.1564</ref><br /> <br /> ==BMAL1==<br /> <br /> ==Heterodimer complex==<br /> <br /> == Circadian Rhythm ==<br /> <br /> The circadian rhythm is the 24 hour protein regulation system found in most mammalian species. The circadian rhythm causes certain proteins to be expressed during the day and then downregulated during the night. The circadian rhythm originates in the suprachiasmatic nucleus (SCN), which is located in the hypothalamus <ref>DOI: 10.1126/science.1222804</ref>. The SCN controls the expression of of proteins in a time dependent manner through a genetic feedback loop initiated by light passing through the eye. The CLOCK:BMAL1 heterodimer complex is a vital component of this system as this heterodimer binds to the E-box promoter region of other circadian rhythm proteins and trigger the transcription of those proteins. These proteins then repress their own transcription in order to regulate the protein content to the appropriate levels.<br /> <ref>DOI: 10.1126/science.1222804</ref><br /> == Disease ==<br /> <br /> Mutated forms of CLOCK exist which do not regulate protein expression correctly and thereby result in altered circadian rhythms. CLOCK-delta19 is a mutant form of CLOCK which binds to BMAL1 normally but the resulting heterodimer does not activate transcription of certain other circadian rhythm proteins.<ref>DOI: 10.1126/science.1222804</ref> Mutant mice carrying this altered CLOCK protein have shown abnormal circadian rhythms as a result.<br /> <br /> It has been shown in recent years that people who have lifestyles which involve light exposure that is different than the normal 12 hours of daylight/12 hours of night have significantly increased chances of developing cancer. This indicates that disruption of the normal circadian rhythm gene regulation cycle has severe downstream effects on the host's genetic makeup.<br /> <br /> == Relevance ==<br /> <br /> == Structural highlights ==<br /> <br /> <scene name='60/609802/Clock-2/1'>CLOCK</scene> and <scene name='60/609802/Bmal1/2'>BMAL1</scene> will form a heterodimer complex.<br /> <br /> This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2067177 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-11-25T18:31:48Z

<p>Joseph Hardie: </p> <hr /> <div>==CLOCK:BMAL1 heterodimer complex==<br /> <br /> <br /> <StructureSection load='4F3L' size='340' side='right' caption='CLOCK:BMAL1 heterodimer complex' scene=''><br /> The CLOCK:BMAL1 heterodimer complex is a vital regulatory component of the circadian rhythm protein regulation system.<br /> This is a default text for your page '''Molecular Playground/CLOCK:BMAL1 heterodimer complex'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br /> You may include any references to papers as in: the use of JSmol in Proteopedia or to the article describing Jmol to the rescue.<br /> <br /> ==CLOCK==<br /> <br /> CLOCK is a protein central to the regulation of the mammalian circadian rhythm system. CLOCK is a helix-loop-helix-PER-ARNT-SIM (bHLH-PAS) protein that regulates the circadian rhythm by forming heterodimers with other circadian rhythm proteins to activate the transcription of other proteins. <br /> <ref>DOI:10.1126/science.280.5369.1564</ref><br /> <br /> ==BMAL1==<br /> <br /> ==Heterodimer complex==<br /> <br /> == Circadian Rhythm ==<br /> <br /> The circadian rhythm is the 24 hour protein regulation system found in most mammalian species. The circadian rhythm causes certain proteins to be expressed during the day and then downregulated during the night. The circadian rhythm originates in the suprachiasmatic nucleus (SCN), which is located in the hypothalamus. The SCN controls the expression of of proteins in a time dependent manner through a genetic feedback loop initiated by light passing through the eye. The CLOCL:BMAL1 heterodimer complex is a vital component of this system as this heterodimer binds to the E-box promoter region of other circadian rhythm proteins and trigger the transcription of those proteins. These proteins then repress their own transcription in order to regulate the protein content to the appropriate levels.<br /> <ref>DOI: 10.1126/science.1222804</ref><br /> == Disease ==<br /> <br /> Mutated forms of CLOCK exist which do not regulate protein expression correctly and thereby result in altered circadian rhythms. CLOCK-delta19 is a mutant form of CLOCK which binds to BMAL1 normally but the resulting heterodimer does not activate transcription of certain other circadian rhythm proteins. Mutant mice carrying this altered CLOCK protein have shown abnormal circadian rhythms as a result.<br /> <br /> It has been shown in recent years that people who have lifestyles which involve light exposure that is different than the normal 12 hours of daylight/12 hours of night have significantly increased chances of developing cancer. This indicates that disruption of the normal circadian rhythm gene regulation cycle has severe downstream effects on the host's genetic makeup.<br /> <br /> == Relevance ==<br /> <br /> == Structural highlights ==<br /> <br /> <scene name='60/609802/Clock-2/1'>CLOCK</scene> and <scene name='60/609802/Bmal1/2'>BMAL1</scene> will form a heterodimer complex.<br /> <br /> This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2067176 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-11-25T18:20:18Z

<p>Joseph Hardie: </p> <hr /> <div>==CLOCK:BMAL1 heterodimer complex==<br /> <br /> <br /> <StructureSection load='4F3L' size='340' side='right' caption='CLOCK:BMAL1 heterodimer complex' scene=''><br /> The CLOCK:BMAL1 heterodimer complex is a vital regulatory component of the circadian rhythm protein regulation system.<br /> This is a default text for your page '''Molecular Playground/CLOCK:BMAL1 heterodimer complex'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br /> You may include any references to papers as in: the use of JSmol in Proteopedia or to the article describing Jmol to the rescue.<br /> <br /> ==CLOCK==<br /> <br /> CLOCK is a protein central to the regulation of the mammalian circadian rhythm system. CLOCK is a helix-loop-helix-PER-ARNT-SIM (bHLH-PAS) protein that regulates the circadian rhythm by forming heterodimers with other circadian rhythm proteins to activate the transcription of other proteins. <br /> <ref>DOI:10.1126/science.280.5369.1564</ref><br /> <br /> ==BMAL1==<br /> <br /> ==Heterodimer complex==<br /> <br /> == Circadian Rhythm ==<br /> <br /> The circadian rhythm is the 24 hour protein regulation system found in most mammalian species. The circadian rhythm causes certain proteins to be expressed during the day and then downregulated during the night. The circadian rhythm originates in the suprachiasmatic nucleus (SCN), which is located in the hypothalamus. The SCN controls the expression of of proteins in a time dependent manner through a genetic feedback loop initiated by light passing through the eye. The CLOCL:BMAL1 heterodimer complex is a vital component of this system as this heterodimer binds to the E-box promoter region of other circadian rhythm proteins and trigger the transcription of those proteins. These proteins then repress their own transcription in order to regulate the protein content to the appropriate levels.<br /> <ref>DOI: 10.1126/science.1222804</ref><br /> == Disease ==<br /> <br /> Mutated forms of CLOCK exist which do not regulate protein expression correctly and thereby result in altered circadian rhythms. CLOCK-delta19 is a mutant form of CLOCK which binds to BMAL1 normally but the resulting heterodimer does not activate transcription of certain other circadian rhythm proteins. Mutant mice carrying this altered CLOCK protein have shown abnormal circadian rhythms as a result.<br /> <br /> == Relevance ==<br /> <br /> == Structural highlights ==<br /> <br /> <scene name='60/609802/Clock-2/1'>CLOCK</scene> and <scene name='60/609802/Bmal1/2'>BMAL1</scene> will form a heterodimer complex.<br /> <br /> This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2067169 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-11-25T17:17:22Z

<p>Joseph Hardie: </p> <hr /> <div>==CLOCK:BMAL1 heterodimer complex==<br /> <br /> <br /> <StructureSection load='4F3L' size='340' side='right' caption='CLOCK:BMAL1 heterodimer complex' scene=''><br /> The CLOCK:BMAL1 heterodimer complex is a vital regulatory component of the circadian rhythm protein regulation system.<br /> This is a default text for your page '''Molecular Playground/CLOCK:BMAL1 heterodimer complex'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br /> You may include any references to papers as in: the use of JSmol in Proteopedia or to the article describing Jmol to the rescue.<br /> <br /> ==CLOCK==<br /> <br /> CLOCK is a protein central to the regulation of the mammalian circadian rhythm system. CLOCK is a helix-loop-helix-PER-ARNT-SIM (bHLH-PAS) protein that regulates the circadian rhythm by forming heterodimers with other circadian rhythm proteins to activate the transcription of other proteins. <br /> <ref>DOI:10.1126/science.280.5369.1564</ref><br /> <br /> ==BMAL1==<br /> <br /> ==Heterodimer complex==<br /> <br /> == Circadian Rhythm ==<br /> <br /> The circadian rhythm is the 24 hour protein regulation system found in most mammalian species. The circadian rhythm causes certain proteins to be expressed during the day and then downregulated during the night. The circadian rhythm originates in the suprachiasmatic nucleus (SCN), which is located in the hypothalamus. The SCN controls the expression of of proteins in a time dependent manner through a genetic feedback loop initiated by light passing through the eye. The CLOCL:BMAL1 heterodimer complex is a vital component of this system as this heterodimer binds to the E-box promoter region of other circadian rhythm proteins and trigger the transcription of those proteins. These proteins then repress their own transcription in order to regulate the protein content to the appropriate levels.<br /> <ref>DOI: 10.1126/science.1222804</ref><br /> == Disease ==<br /> <br /> == Relevance ==<br /> <br /> == Structural highlights ==<br /> <br /> <scene name='60/609802/Clock-2/1'>CLOCK</scene> and <scene name='60/609802/Bmal1/2'>BMAL1</scene> will form a heterodimer complex.<br /> <br /> This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2067160 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-11-25T16:46:48Z

<p>Joseph Hardie: </p> <hr /> <div>==CLOCK:BMAL1 heterodimer complex==<br /> <br /> <br /> <StructureSection load='4F3L' size='340' side='right' caption='CLOCK:BMAL1 heterodimer complex' scene=''><br /> The CLOCK:BMAL1 heterodimer complex is a vital regulatory component of the circadian rhythm protein regulation system.<br /> This is a default text for your page '''Molecular Playground/CLOCK:BMAL1 heterodimer complex'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br /> You may include any references to papers as in: the use of JSmol in Proteopedia or to the article describing Jmol to the rescue.<br /> <br /> ==CLOCK==<br /> <br /> CLOCK is a protein central to the regulation of the mammalian circadian rhythm system. CLOCK is a helix-loop-helix-PER-ARNT-SIM (bHLH-PAS) protein that regulates the circadian rhythm by forming heterodimers with other circadian rhythm proteins to activate the transcription of other proteins. <br /> <ref>DOI:10.1126/science.280.5369.1564</ref><br /> <br /> ==BMAL1==<br /> <br /> ==Heterodimer complex==<br /> <br /> == Circadian Rhythm ==<br /> <br /> The circadian rhythm is the 24 hour protein regulation system found in most mammalian species. The circadian rhythm causes certain proteins to be expressed during the day and then downregulated during the night. The circadian rhythm originates in the suprachiasmatic nucleus (SCN), which is located in the hypothalamus. The SCN controls the expression of of proteins in a time dependent manner through a genetic feedback loop initiated by light passing through the eye. <br /> <ref>DOI: 10.1126/science.1222804</ref><br /> == Disease ==<br /> <br /> == Relevance ==<br /> <br /> == Structural highlights ==<br /> <br /> <scene name='60/609802/Clock-2/1'>CLOCK</scene> and <scene name='60/609802/Bmal1/2'>BMAL1</scene> will form a heterodimer complex.<br /> <br /> This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2066495 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-11-24T04:22:55Z

<p>Joseph Hardie: </p> <hr /> <div>==CLOCK:BMAL1 heterodimer complex==<br /> <br /> <br /> <StructureSection load='4F3L' size='340' side='right' caption='CLOCK:BMAL1 heterodimer complex' scene=''><br /> The CLOCK:BMAL1 heterodimer complex is a vital regulatory component of the circadian rhythm protein regulation system.<br /> This is a default text for your page '''Molecular Playground/CLOCK:BMAL1 heterodimer complex'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br /> You may include any references to papers as in: the use of JSmol in Proteopedia or to the article describing Jmol to the rescue.<br /> <br /> ==CLOCK==<br /> <br /> CLOCK is a protein central to the regulation of the mammalian circadian rhythm system. CLOCK regulates the circadian rhythm by forming heterodimers with other circadian rhythm proteins to activate the transcription of other proteins.<br /> <ref>DOI:10.1126/science.280.5369.1564</ref><br /> <br /> ==BMAL1==<br /> <br /> ==Heterodimer complex==<br /> <br /> == Circadian Rhythm ==<br /> <ref>DOI: 10.1126/science.1222804</ref><br /> == Disease ==<br /> <br /> == Relevance ==<br /> <br /> == Structural highlights ==<br /> <br /> <scene name='60/609802/Clock-2/1'>CLOCK</scene> and <scene name='60/609802/Bmal1/2'>BMAL1</scene> will form a heterodimer complex.<br /> <br /> This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2066494 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-11-24T03:58:04Z

<p>Joseph Hardie: </p> <hr /> <div>==CLOCK:BMAL1 heterodimer complex==<br /> <br /> <br /> <StructureSection load='4F3L' size='340' side='right' caption='CLOCK:BMAL1 heterodimer complex' scene=''><br /> The CLOCK:BMAL1 heterodimer complex is a vital regulatory component of the circadian rhythm protein regulation system.<br /> This is a default text for your page '''Molecular Playground/CLOCK:BMAL1 heterodimer complex'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br /> You may include any references to papers as in: the use of JSmol in Proteopedia or to the article describing Jmol to the rescue.<br /> <br /> ==CLOCK==<br /> <br /> <ref>DOI:10.1126/science.280.5369.1564</ref><br /> <br /> ==BMAL1==<br /> <br /> ==Heterodimer complex==<br /> <br /> == Function ==<br /> <ref>DOI: 10.1126/science.1222804</ref><br /> == Disease ==<br /> <br /> == Relevance ==<br /> <br /> == Structural highlights ==<br /> <br /> <scene name='60/609802/Clock-2/1'>CLOCK</scene> and <scene name='60/609802/Bmal1/2'>BMAL1</scene> will form a heterodimer complex.<br /> <br /> This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2066454 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-11-23T23:15:56Z

<p>Joseph Hardie: </p> <hr /> <div>==CLOCK:BMAL1 heterodimer complex==<br /> <br /> <br /> <StructureSection load='4F3L' size='340' side='right' caption='CLOCK:BMAL1 heterodimer complex' scene=''><br /> The CLOCK:BMAL1 heterodimer complex is a vital regulatory component of the circadian rhythm protein regulation system.<br /> This is a default text for your page '''Molecular Playground/CLOCK:BMAL1 heterodimer complex'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br /> You may include any references to papers as in: the use of JSmol in Proteopedia or to the article describing Jmol to the rescue.<br /> <br /> ==CLOCK==<br /> <br /> ==BMAL1==<br /> <br /> ==Heterodimer complex==<br /> <br /> == Function ==<br /> <ref>DOI: 10.1126/science.1222804</ref><br /> == Disease ==<br /> <br /> == Relevance ==<br /> <br /> == Structural highlights ==<br /> <br /> <scene name='60/609802/Clock-2/1'>CLOCK</scene> and <scene name='60/609802/Bmal1/2'>BMAL1</scene> will form a heterodimer complex.<br /> <br /> This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2065635 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-11-19T18:13:35Z

<p>Joseph Hardie: </p> <hr /> <div>==CLOCK:BMAL1 heterodimer complex==<br /> <br /> <StructureSection load='4F3L' size='340' side='right' caption='CLOCK:BMAL1 heterodimer complex' scene=''><br /> This is a default text for your page '''Molecular Playground/CLOCK:BMAL1 heterodimer complex'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br /> You may include any references to papers as in: the use of JSmol in Proteopedia or to the article describing Jmol to the rescue.<br /> <br /> ==CLOCK==<br /> <br /> ==BMAL1==<br /> <br /> ==Heterodimer complex==<br /> <br /> == Function ==<br /> <ref>DOI: 10.1126/science.1222804</ref><br /> == Disease ==<br /> <br /> == Relevance ==<br /> <br /> == Structural highlights ==<br /> <br /> This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2065627 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-11-19T18:11:04Z

<p>Joseph Hardie: </p> <hr /> <div>==CLOCK:BMAL1 heterodimer complex==<br /> <br /> <StructureSection load='4F3L' size='340' side='right' caption='CLOCK:BMAL1 heterodimer complex' scene=''><br /> This is a default text for your page '''Molecular Playground/CLOCK:BMAL1 heterodimer complex'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br /> You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br /> <br /> ==CLOCK==<br /> <br /> ==BMAL1==<br /> <br /> ==Heterodimer complex==<br /> <br /> == Function ==<br /> <ref>DOI: 10.1126/science.1222804</ref><br /> == Disease ==<br /> <br /> == Relevance ==<br /> <br /> == Structural highlights ==<br /> <br /> This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2065621 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-11-19T18:10:27Z

<p>Joseph Hardie: </p> <hr /> <div>==CLOCK:BMAL1 heterodimer complex==<br /> ==CLOCK==<br /> <StructureSection load='4F3L' size='340' side='right' caption='CLOCK:BMAL1 heterodimer complex' scene=''><br /> This is a default text for your page '''Molecular Playground/CLOCK:BMAL1 heterodimer complex'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br /> You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br /> <br /> ==BMAL1==<br /> <br /> ==Heterodimer complex==<br /> <br /> == Function ==<br /> <ref>DOI: 10.1126/science.1222804</ref><br /> == Disease ==<br /> <br /> == Relevance ==<br /> <br /> == Structural highlights ==<br /> <br /> This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2065612 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-11-19T18:08:55Z

<p>Joseph Hardie: </p> <hr /> <div>==CLOCK==<br /> <StructureSection load='4F3L' size='340' side='right' caption='CLOCK:BMAL1 heterodimer complex' scene=''><br /> This is a default text for your page '''Molecular Playground/CLOCK:BMAL1 heterodimer complex'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br /> You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br /> <br /> ==BMAL1==<br /> <br /> ==Heterodimer complex==<br /> <br /> == Function ==<br /> <ref>DOI: 10.1126/science.1222804</ref><br /> == Disease ==<br /> <br /> == Relevance ==<br /> <br /> == Structural highlights ==<br /> <br /> This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2065602 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-11-19T18:06:52Z

<p>Joseph Hardie: </p> <hr /> <div>==Your Heading Here (maybe something like 'Structure')==<br /> <StructureSection load='4F3L' size='340' side='right' caption='CLOCK:BMAL1 heterodimer complex' scene=''><br /> This is a default text for your page '''Molecular Playground/CLOCK:BMAL1 heterodimer complex'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br /> You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br /> <br /> == Function ==<br /> <ref>DOI: 10.1126/science.1222804</ref><br /> == Disease ==<br /> <br /> == Relevance ==<br /> <br /> == Structural highlights ==<br /> <br /> This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Molecular_Playground/CLOCK:BMAL1_heterodimer_complex&diff=2065583 Molecular Playground/CLOCK:BMAL1 heterodimer complex 2014-11-19T17:59:13Z

<p>Joseph Hardie: New page: ==Your Heading Here (maybe something like 'Structure')== <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> This is a default text for you...</p> <hr /> <div>==Your Heading Here (maybe something like 'Structure')==<br /> <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''><br /> This is a default text for your page '''Molecular Playground/CLOCK:BMAL1 heterodimer complex'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br /> You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br /> <br /> == Function ==<br /> <br /> == Disease ==<br /> <br /> == Relevance ==<br /> <br /> == Structural highlights ==<br /> <br /> This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Joseph_Hardie/Sandbox_1&diff=2065564 Joseph Hardie/Sandbox 1 2014-11-19T17:44:44Z

<p>Joseph Hardie: </p> <hr /> <div>==Your Heading Here (maybe something like 'Structure')<br /> == Headline text ==<br /> ==<br /> <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''><br /> This is a default text for your page '''Joseph Hardie/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br /> You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br /> <br /> == Function ==<br /> <br /> == Disease ==<br /> <br /> == Relevance ==<br /> <br /> == Structural highlights ==<br /> <br /> This is a [[sample scen]]e created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> <scene name='60/609791/Franklin/1'>what</scene>><br /> [[Link title]]<br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Joseph_Hardie/Sandbox_1&diff=2065558 Joseph Hardie/Sandbox 1 2014-11-19T17:43:25Z

<p>Joseph Hardie: </p> <hr /> <div>==Your Heading Here (maybe something like 'Structure')<br /> == Headline text ==<br /> ==<br /> <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''><br /> This is a default text for your page '''Joseph Hardie/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br /> You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br /> <br /> == Function ==<br /> <br /> == Disease ==<br /> <br /> == Relevance ==<br /> <br /> == Structural highlights ==<br /> <br /> This is a [[sample scen]]e created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> scene name='60/609791/Franklin/1'>what</scene><br /> [[Link title]]<br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Joseph_Hardie/Sandbox_1&diff=2065516 Joseph Hardie/Sandbox 1 2014-11-19T17:32:09Z

<p>Joseph Hardie: </p> <hr /> <div>==Your Heading Here (maybe something like 'Structure')<br /> == Headline text ==<br /> ==<br /> <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''><br /> This is a default text for your page '''Joseph Hardie/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br /> You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br /> <br /> == Function ==<br /> <br /> == Disease ==<br /> <br /> == Relevance ==<br /> <br /> == Structural highlights ==<br /> <br /> This is a [[sample scen]]e created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> <br /> [[Link title]]<br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Joseph_Hardie/Sandbox_1&diff=2065509 Joseph Hardie/Sandbox 1 2014-11-19T17:30:54Z

<p>Joseph Hardie: </p> <hr /> <div>==Your Heading Here (maybe something like 'Structure')<br /> == Headline text ==<br /> ==<br /> <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''><br /> This is a default text for your page '''Joseph Hardie/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br /> You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br /> <br /> == Function ==<br /> <br /> == Disease ==<br /> <br /> == Relevance ==<br /> <br /> == Structural highlights ==<br /> <br /> This is a [[sample scen]]e created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie https://proteopedia.org/index.php?title=Joseph_Hardie/Sandbox_1&diff=2065491 Joseph Hardie/Sandbox 1 2014-11-19T17:27:40Z

<p>Joseph Hardie: New page: ==Your Heading Here (maybe something like 'Structure')== <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> This is a default text for you...</p> <hr /> <div>==Your Heading Here (maybe something like 'Structure')==<br /> <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''><br /> This is a default text for your page '''Joseph Hardie/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the &lt; and &gt; signs.<br /> You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.<br /> <br /> == Function ==<br /> <br /> == Disease ==<br /> <br /> == Relevance ==<br /> <br /> == Structural highlights ==<br /> <br /> This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> </StructureSection><br /> == References ==<br /> <references/></div>

Joseph Hardie