Proteopedia - User contributions [en]

Molecular Playground/Hemoglobin-Haptoglobin Complex

2014-12-18T01:16:41Z

Ololade Fatunmbi: New page: One of the CBI Molecules being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display ...

One of the [[CBI Molecules]] being studied in the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program] at UMass Amherst and on display at the [http://www.molecularplayground.org/ Molecular Playground].

[[Image:Newpathwayblackpng-Recovered2.png|thumb|400px|right| Figure 1. Hb-Hp/CD-163 Pathway during Intravascular hemolysis by Ololade Fatunmbi. Haptoglobin 1-1 (Hp), an abundant glycoprotein in blood binds free hemoglobin (Hb) dimers in one of the strongest non-covalent binding events known in biology. This interaction shields Hb residues that are prone to oxidative modification. Hb-Hp globin complexes bind to the CD163 cell surface receptor on macrophages leading to their internalization and catabolism. ]]

<table align="right" width="300" border="0" style="background-color:#e0e0e0;"><tr><td>
<Structure load=‘4f4o’ size='350' frame='true' align='right' caption='HbHp’ scene='60/609783/Hbhpdimerblack/5'/>
</td></tr>
<tr><td>
<center><scene name='60/609783/Hbhpdimerblack/5'>Porcine Hemoglobin-Haptoglobin Complex Molecular Playground</scene> Color Code:</center>
<table border="2">
<tr>
<td>Haptoglobin (Hp) Magenta </td>
<td>Hemoglobin α-chain Cyan</td>
<td>Hemoglobin β-Chain Lime Green </td>
</tr>
<tr>
<td>Hp:<scene name='60/609783/Hbhpmonomer/13'> CD163 (HbHp receptor) recognition loop </scene>(silver)</td>
<td>Hb: <scene name='60/609783/Hbdimerfromhbhp/4'>Redox active residues</scene> (blue spheres)</td>
<td>HbHp complex: Residues involved in <scene name='60/609783/Hbhpmonomer/14'>salt bridges</scene> & <scene name='60/609783/Hbhpmonomer/16'>other electrostatic interactions</scene> (bold)</td>
</tr>
</table>

</td></tr></table>

==Summary==

[http://en.wikipedia.org/wiki/Hemoglobin ''Hemoglobin''] (Hb) is arguably one of the most studied proteins of all time. Hb is essential for our lives and nearly all other vertebrates because it transports oxygen from organs to tissues so that we can have energy. However, like most entities in life, too much of something may actually be harmful. In a process called [http://en.wikipedia.org/wiki/Hemolytic_anemia ''intravascular hemolysis''], high concentrations of Hb are released from red blood cells into the extracellular environment, which could cause [http://en.wikipedia.org/wiki/redox ''oxidative''] damage to our tissues [1]. [http://en.wikipedia.org/wiki/haptoglobin ''Haptoglobin''] (Hp), an [http://en.wikipedia.org/wiki/Acute-phase_protein ''acute phase''] glycoprotein, counteracts the negative physiological consequences of intravascular hemolysis by binding Hb [2-4] in one of strongest non-covalent events known in nature (Kd ~1 × 10–15 mol/L) [5,6]. See Figure 1.
==Function==
Hb physiologically exists as a <scene name='60/609783/Hbtetramer/2'>tetramer</scene> (Hbα1β1α2β2) found in red blood cells. During intravascular hemolysis, red blood cells (erythrocytes) rupture. Hb is then released into the [http://en.wikipedia.org/wiki/extracellular ''extracellular''] environment, and could be come very toxic to the body by causing severe oxidative tissue damage. Hb subunits dissociate into dimers (Hbα1β1) in the extracellular environment exposing <scene name='60/609783/Hbdimerfromhbhp/4'> residues that are prone to oxidative modification</scene> [10]. In addition, heme, the prosthetic group on Hb could react with hydrogen peroxide to generate [http://en.wikipedia.org/wiki/Reactive_oxygen_species ''reactive oxygen species''] (ROS) through [http://en.wikipedia.org/wiki/Haber–Weiss_reaction '' Fenton and Haber-Weiss reactions''] and the iron present in heme catalyzes these reactions [3]. See Figure 2. Moreover, both the protein and heme regions of free Hb could cost excessive oxidative damage to the body by reacting with small molecules in circulation such as hydrogen peroxide. Extracellular Hb, could also react irreversibly with nitric oxide (NO), a critical regulator of smooth muscle tone and platelet activation [2]. The consumption of NO by Hb leads to limited bioavailability of NO and the production of nitrate and [http://en.wikipedia.org/wiki/methemoglobin ''methemoglobin''] [2].<scene name='60/609783/Hbhpmonomer/10'> Hp binding shields Hb </scene>and exposes a <scene name='60/609783/Hbhpmonomer/13'> neoepiptope</scene> recognized by the multifunctional receptor, CD163. The Hb-Hp complex binds CD-163 with high affinity and mediates haptoglobin-hemoglobin [http://en.wikipedia.org/wiki/endocytosis ''endocytosis''] and degradation [4].[[Image:Reaction.png |thumb|400px|right| Figure 2. Reactions of iron and hydrogen peroxide generate reactive oxygen species generated by [3]. Blue spheres indicate radicals.]]
<rb>Hp is found in nearly all mammals and some vertebrates. In humans, there are two allelic forms, Hp1 and Hp2, which manifest three phenotypes [2]. Hp1 is responsible for the Hp1-1 phenotype. Partial intragenic duplication in Hp1 gives rise to Hp2 allele, which is responsible for two phenotypes, Hp2-1 and Hp2-2 [1,2]. Both in vitro and in vivo studies have established that subjects with the Hp1-1 phenotype are more likely to resist cellular oxidative stress than those with the Hp2-2 phenotype, with Hp2-1 being intermediate [7].

== Structural Highlights ==
Haptoglobin 
The alone crystal structure of Hp has not yet been elucidated. Hp1-1 is ~90kda and exists as a <scene name='60/609783/Hpdimerblack/11'>heterodimer</scene> consisting of the two light chains and two heavy chains. The light chains are linked by the disulfide bond formed between <scene name='60/609783/Hpdimerblack/16'>Cys 33-Cys 33</scene>. Altogether there are 4 disulfides bonds on Hp and the <scene name='60/609783/Hpdimerblack/15'>Cys 90-Cys 207</scene> bond hold the light and heavy chains of Hp together. There are also <scene name='60/609783/Hpdimerblack/6'>4 n-linked glycosylation sites</scene> found on each monomer of Hp1-1 [8].
 
The light chain of Hp shares high homology with [http://en.wikipedia.org/wiki/Complement_control_protein ''complement control proteins''] while the heavy chain is very homologous with [http://en.wikipedia.org/wiki/serine_protease ''serine proteases''] [1]. Although Hp is not an active protease, the Hb-binding site in Hp is located in the region responsible for substrate specificity in other serine proteases (17). In serine proteases, the typical active-site residues are -histidine-57 and serine-195. In Hp these residues are replaced by lysine and alanine, respectively [9]). However, a substrate specific residue in trypsin <scene name='60/609783/Hpdimerblack/19'>aspartic acid-189</scene> does occur in Hp [9].
 
Hemoglobin-Haptoglobin Complex 
What makes the binding between Hp so tight and nearly irreversible? Recently, the crystal structure of porcine Hb-Hp was solved and revealed interactions involved in Hb-Hp interface [1]. Porcine Hp shares 82% homology with human Hp 1-1 [1,10]. The interaction between Hb and Hp is composed of various hydrophobic and <scene name='60/609783/Hbhpmonomer/14'>salt bridges</scene> and <scene name='60/609783/Hbhpmonomer/16'>other electrostatic interactions</scene> [10].

== Disease ==

Prevention of Renal Damage: Intravascular hemolysis occurs in several diseases including [http://en.wikipedia.org/wiki/Sickle-cell_disease ''sickle-cell anemia''] and [http://en.wikipedia.org/wiki/Malaria ''malaria''] [1]. Another consequence caused by free hemoglobin is oxidative damage in renal tissues following intravascular hemolysis [7]. Yet when haptoglobin binds to hemoglobin, the complex is too large to pass through the glomeruli of the kidney and will be removed via the reticuloendothelial system [7]. Therefore Hb induced injury to the parenchyma is prevented by haptoglobin [11]. 
 
Antibacterial Activity: When hemoglobin becomes non-covalently bound to haptoglobin, Hb and iron are no longer available to Escherichia coli and other bacteria that require iron [7]. Eaton was able to demonstrate that when Hp was given to rats that have been intraperitoneally injected with E. Coli and hemoglobin, Hp was able to prevent fatal effects [12].
 
Antioxidant Activity: Haptoglobin has a significant role as an [http://en.wikipedia.org/wiki/antioxidant ''antioxidant''] [13]. Free Hb also increases the peroxidation of purified [http://en.wikipedia.org/wiki/Arachidonic_acid ''arachidonic acid''] and other [http://en.wikipedia.org/wiki/polyunsaturated_fatty_acids ''polyunsaturated fatty acids''] within neuronal cell membranes (10). Iron released from heme proteins can catalyze oxidative injury to neuronal cell membranes and might have a role in posttraumatic central nervous system (CNS) damage [14]. Haptoglobin, binds to Hb and removes it from the circulation and prevents iron-stimulated formation of oxygen radicals [15].

== Relevance ==

Hp has developed of a lot interest in drug therapy development recently because of its effectiveness in detoxifying free Hb activity when hemolytic related events occur in diseases [16-20] such as sickle cell anemia [16].

== Research Interests ==

[http://www.chem.umass.edu/people/kaltashovlab/ Kaltashov Lab]: We are a Biological Mass Spectrometry group at the University of Massachusetts, Amherst. Our research is focused on developing mass spectrometry-based strategies to study protein architecture, dynamics, and interactions with small molecules and other biopolymers. [http://www.chem.umass.edu/people/kaltashovlab/graduatestudents.html ''Ololade Fatunmbi'] (Graduate Assistant Researcher) 
Studies of the Hp mediated Hb clearance pathway suggest that Hp may be used for targeted drug delivery. This use requires a detailed understanding of conformational dynamics and interactions in this protein/receptor system. However, Hb-Hp/CD163 complex crystal structure and conformational dynamics have not yet been determined. I focus on studyingatomic level predictions of Hb-Hp/CD163 protein interactions and conformational dynamics using bioinformatics techniques and native mass spectrometry.
 
[http://www.chem.umass.edu/people/kaltashovlab/undergraduateresearchers.html ''Chibueze Egeruoh''] (Undergraduate Assistant Researcher) African trypanosomiasis or sleeping sickness is a parasitic disease of humans and other animals. On the structures of African trypanosomes, there is a coat of surface monolayer of variant surface glycoprotein (VSG) that protects the parasite. Within the VSG coat there are HbHp receptors that have the purposes of binding Hb-Hp acquisition heme through endocytosis so that the parasite would have nutrients such as iron present in Hb. Understanding the interaction of Hb-Hp complexes and trypanosome receptors will improve drug delivery to susceptible trypanosomes parasite. I conduct molecular modeling studies on trypanosome receptors and docking studies on Hb-Hp african trypanosoma receptors in complex with Hb-Hp complexes.
== References ==
<references/>
[http://www.ncbi.nlm.nih.gov/pubmed/11196644 1. Kristiansen M, Graversen JH, Jacobsen C, et al. Identification of the haemoglobin scavenger re- ceptor. Nature. 2001;409:198-201.] 
[http://www.ncbi.nlm.nih.gov/pubmed/19380867 2. Marianne Jensby Nielsen and Søren Kragh Moestrup. Receptor targeting of hemoglobin mediated by the haptoglobins: roles beyond heme scavenging. Blood. 2009. 114:764-771] 
[http://www.ncbi.nlm.nih.gov/pubmed/18486167 3. Isaac K. Quaye. Haptoglobin, inflammation and disease Trans R Soc Trop Med Hyg. 2008; 102, 735—742.] 
[http://www.ncbi.nlm.nih.gov/pubmed/20299103 4. Hanne Van Gorp, et al. Scavenger receptor CD-163, a Jack-of-all-trades and potential target for cell-directed therapy. Molecular Immunology. 2010; 47: 1650–1660.] 
[http://www.ncbi.nlm.nih.gov/pubmed/6751044 5. Bowman, BH, Kurosky, A: Haptoglobin: The evolutionary product of duplication, unequal crossing over, and point mutation. Adv Hum Genet 1982 12:189–261] 
[http://www.ncbi.nlm.nih.gov/pubmed/2073325 6. McCormick, DJ, Atassi, MZ: Hemoglobin binding with haptoglobin: Delineation of the haptoglobin binding site on the alpha-chain of human hemoglobin. J Protein Chem 1990 9:735–742] 
[http://www.ncbi.nlm.nih.gov/pubmed/15298155 7. S.M. Hossein Sadrzadeh, PhD, and Jafar Bozorgmehr, MD. Haptoglobin Phenotypes in Health and Disorders. Am J Clin Pathol. 2004; 121: 97-104] 
[http://www.ncbi.nlm.nih.gov/pubmed/172407 8. Black JA, Dixon GH. Amino-acid sequence of alpha chains of human haptoglobins. Nature. 1968;218:738-741.] 
[http://www.ncbi.nlm.nih.gov/pubmed/6997877 9. Alexander Kurosky et al. Covalent structure of human haptoglobin: A serine protease homolog. Biochemistry. 1980; 77: 3388-3392.] 
[http://www.ncbi.nlm.nih.gov/pubmed/22922649 10. Christian Brix Folsted Andersen. Structure of the haptoglobin–haemoglobin complex. Nature. 2012; 489: 456-459] 
[http://www.ncbi.nlm.nih.gov/pubmed/400530 11. Javid J. Human haptoglobins. Curr Top Hematol. 1978;1:151- 192.] 
[http://www.ncbi.nlm.nih.gov/pubmed/7036344 12. Eaton, et al. Haptoglobin: A natural bacteriostat. Science. 1982. 215: 691–693] 
[http://www.ncbi.nlm.nih.gov/pubmed/1476417 13. Lange V. Haptoglobin polymorphism: not only a genetic marker. Anthropol Anz. 1992;50:281-302.] 
[http://www.ncbi.nlm.nih.gov/pubmed/6094553 14. Sadrzadeh SMH, Graf E, Panter SS, et al. Hemoglobin: a biologic Fenton reagent. J Biol Chem. 1984;259:14354-14356 ] 
[http://www.ncbi.nlm.nih.gov/pubmed/8087243 15. Vercellotti GM, Balla G, Balla J, et al. Heme and the vasculature: an oxidative hazard that induces antioxidant defenses in the endothelium. Artif Cells Blood Substit Immobil Biotechnol. 1994;22:207-213.] 
[http://www.ncbi.nlm.nih.gov/pubmed/23140673 16. A. I. Alayash, C. B. Andersen, S. K. Moestrup, and L. Bülow. (2013) Haptoglobin: the hemoglobin detoxifier in plasma. Trends Biotechno,31. 2–3] 
[http://www.ncbi.nlm.nih.gov/pubmed/7865954 17. Gando S, Tedo I. (1994) The effects of massive transfusion and haptoglobin therapy on hemolysis in trauma patients. Surg Today. 9. 785-790.] 
[http://www.wiley.com/WileyCDA/WileyTitle/productCd-0470924314.html 18. Joseph Bertolini, Neil Goss, John Curling (2012) Production of Plasma Proteins for Therapeutic Use. Biochemistry; Edition 1: 332.] 
[http://www.ncbi.nlm.nih.gov/pubmed/8163802 19. Imaizumi H, Tsunoda K, Ichimiya N, Okamoto T, Namiki A. Repeated large-dose haptoglobin therapy in an extensively burned patient: case report. J Emerg Med 1994;12(1):33-37.] 
[http://www.ncbi.nlm.nih.gov/pubmed/23264591 20. D. J. Schaer, P. W. Buehler, A. I. Alayash, et,. al Hemolysis and free hemoglobin revisited: exploring hemoglobin and hemin scavengers as a novel class of therapeutic proteins. Blood. 121.8:1276–1284, 2013]

== Acknowledgements==
Ololade Fatunmbi and Chibueze Egeruoh [http://www.chem.umass.edu/people/kaltashovlab/ (Kaltashov Lab)] 
PDB ID:4F4O from [http://www.rcsb.org/pdb/explore.do?structureId=4f4O Anderson, CB ''et. al'' (2012. Nature)]

CBI Molecules

2014-12-18T01:15:36Z

Ololade Fatunmbi:

These are molecules under study by members of the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program].
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.

UMass CBI Members, add your molecules to the list (which is alphabetical by CBI research mentor); follow the instructions below the list.

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).
Follow the instructions at the bottom of this page.

==Molecules==
'''** Designates CBI Molecules Featured on [http://www.umass.edu/cbi/ CBI website]'''

[http://chamberslab.com/wp/ Chambers Lab]

: '''[[Molecular Playground/Glutamate Receptor]]''', Amanda Hussey, Steve McCarron, Rosie Combs-Bachmann, Mariel Feliciano

[http://www.chem.umass.edu/~chenlab/index.HTML Chen Lab]

: '''[[Molecular Playground/ClyA]]''', Monifa Fahie, Bib Yang '''Revised 2014'''
: '''[[Molecular Playground/OmpG]]''', Christina Chisholm, Monifa Fahie, Bib Yang '''Revised 2014'''

[http://openwetware.org/wiki/Chien Chien Lab]

: '''[[Molecular Playground/ClpP]]''', Lisa Hernandez, Rob Vass '''New 2014'''
: '''[[Molecular Playground/Homo-dimeric RcdA]]''', Kamal K. Joshi
: **'''[[Molecular Playground/Hexameric ClpX]]''', Joanne Lau '''Best CBI Molecule 2011'''
: '''[[Molecular Playground/DNA replication initiator DnaA]]''', Jing Liu

Farkas Lab
: '''[[Molecular Playground/CLOCK:BMAL1 heterodimer complex]]''', Hui-Hsien Lin, Joseph Hardie, Michael Mingroni '''New 2014'''

Forbes Lab

: '''[[Molecular Playground/CheR]]''', Miaomin Zhang
: '''[[Molecular Playground/RBP]]''', Jan Panteli
: '''[[Molecular Playground/TRAIL]]''', Charley Swofford

[http://www.biochem.umass.edu/garman/index.html Garman Lab]

: '''[[Molecular Playground/Human Protective Protein Cathepsin A]]''', Yadilette Rivera-Colon
: '''[[Molecular Playground/Human PPCA]]''', Nilima Kolli

[http://people.chem.umass.edu/gieraschlab/ Gierasch Lab]

: '''[[Molecular_Playground/DnaK]]''', Joseph Tilitsky, New 2014
: '''[[CRABP I ( Cellular Retinoic Acid Binding Protein )|Molecular Playground/CRABP I]]''', Kristine Faye Pobre, Mylene Ferrolino,Mangai Periasamy '''Best Overall CBI Molecule 2010'''
: '''[[Molecular Playground/CRABP I (Cellular Retinoic Acid Binding Protein)]]''', Gustavo Elberto Epalza Sanchez
: **'''[[Molecular_Playground/DHFR]]''', Karan Hingorani '''Best CBI Molecule 2012'''

[http://people.chem.umass.edu/jhardy/ Hardy Lab]

: '''[[Molecular Playground/Executioner Caspase-7]]''', Derek MacPherson, Maureen E. Hill
: '''[[Molecular Playground/Caspase-3 Regulatory Mechanisms]]''', Scott Eron, Bay Serrano, Yunlong Zhao
: '''[[Molecular Playground/Caspase-6 and neurodegeneration]]''', Kevin Buadlart Dagbay
: '''[[Molecular Playground/Caspase-7 Dynamics]]'''
: '''[[Molecular Playground/Caspase-9 Regulation]]''', Kristen Huber
: '''[[Molecular Playground/Caspase-6 (new)]]''', Elih Velazquez
: '''[[Molecular Playground/Influenza A M2 transmembrane domain]]''', Samantha Nicholls
: '''[[Molecular Playground/Dengue Virus Protease]]''', Muslum Yildiz

Hebert Lab

: '''[[Molecular_Playground/Hsp70-Hsp90]]''', Jill Graham "Revised 2014"
: '''[[Molecular_Playground/ERDj5]]''', Lydia Lamriben
: '''[[Molecular Playground/Saposin C]]''', Abla Tannous
: '''[[Molecular_Playground/ERMan1]]''', Johan Sunryd

[http://people.biochem.umass.edu/aheuck/aph.html Heuck Lab]

: '''[[Molecular_Playground/Pcr H]]''', Fabian Romano, Carolina Morell-Pérez, Yuzhou Tang

[http://people.chem.umass.edu/mholden/ Holden Lab]

: '''[[Molecular Playground/Protective Antigen]]''', Jing Huang

[http://www.chem.umass.edu/people/kaltashovlab/ Kaltashov Lab]
: '''[[Molecular Playground/Hemoglobin-Haptoglobin Complex]]''', Ololade Fatunmbi, Chibueze Egeruoh '''***New Fall 2014***'''
: '''[http://proteopedia.org/wiki/index.php/Chengfeng_Ren Molecular Playground/Inteferon]'''[Revised], Chengfeng Ren
: ''' [[Molecular Playground/Transferrin]]''', Khaja Muneeruddin, Jake Pawlowski
: '''[[Molecular Playground/Velaglucerase]]''', Adriana Kita
: '''[[Molecular Playground/Antithrombin-Heparin]]''', Yunlong Zhao

[http://people.chem.umass.edu/knapplab/?q=knappchem/index.html/ Knapp Lab]
: '''[[Molecular Playground/Prolyl Hydroxylase Domain (PHD) Enzyme]]''', Cristina Martin, Serap Pektas '''Best CBI Molecule Proteopedia Page 2010''' '''***New Fall 2014***'''
: '''[[Molecular Playground/FIH]]''', Vanessa Chaplin, Cornelius Taabazuing, Breanne Holmes, John Hangasky

[http://people.chem.umass.edu/mmaroney/ Maroney Lab]

: '''[[Molecular Playground/UreE]]''', Priyanka Basak, '''New 2014'''
: '''[[Molecular Playground/Nickel Superoxide Dismutase]]''', Carolyn Carr
: '''[[Molecular Playground/CsoR and RcnR]]''', Heidi Hu, Carolyn Carr, Hsin-Ting (Tiffany )Huang, '''Revised 2014'''
: '''[[Molecular Playground/HypA]]''', Heidi Hu

[http://www.chem.umass.edu/~cmartin/ Martin Lab]

: **'''[[Molecular Playground/T7 RNAP Conformations]]''', Luis E. Ramirez-Tapia '''Best CBI Molecule 2011'''
: '''[[Molecular Playground/T7 RNA Polymerase (7 mer int)]]''', Ankit Vahia
: '''[[Molecular Playground/Human mtRNA pol]]''', Ketan Mathavan

[http://www.peytonlab.org/ Peyton Lab]
: '''[[Molecular Playground/IntegrinBeta1]]''', Lauren Jansen, Lauren Barney, Elizabeth Brooks, Alyssa Schwartz ***'''NEW FALL 2014''''***
: '''[[Molecular Playground/MMP14]]''', Lauren Jansen
: '''[[Molecular Playground/C-Raf]]''', Thuy Nguyen
: '''[[Molecular Playground/FAK]]''', Dannielle Ryman

[http://roberts.openwetware.org/ Roberts Lab]

: '''[[Molecular Playground/Taxol]]''', Elizabeth Cummings, Rohan Patil, Sarah Wilson ***'''Revised Fall 2014'''***
: '''[[Molecular Playground/Insulin]]''', Whitney Stoppel

[http://www.umass.edu/rotellogroup/ Rotello Lab]

: '''[[Reverse transcriptase|Molecular Playground/Reverse Transcriptase]]''', Daniel Moyano-Marino
: '''[[Molecular Playground/Pancreatic Lipase]]''', Rui Tang
: '''[[Molecular playground/Chymotrypsin]]''', Brad
: '''[[Molecular Playground/Targeting Peptide]]''', David Solfiell

[http://http://www.umass.edu/schiffman/ Schiffman Lab]
: '''[[Molecular Playground/Streptavidin]]''', Katrina Rieger

[http://www.biochem.umass.edu/faculty/danny-j-schnell Schnell Lab]
: '''[[Molecular Playground/Tic40]]''', Mine Canakci

Tew Lab

: '''[[Molecular Playground/HIV Tat]]''', Brittany deRonde, Coralie Backlund

Thayumanavan Lab
: '''[[Interleukin-1 beta]]''', Huan He
: '''[[Molecular Playground/Lysozyme ]]''', Daniella Gonzalez
: '''[[Molecular Playground/Beta-galactosidase]]''', Judy Ventura
: '''[[User:Krishna Reddy Ragupathi|Molecular Playground/Carbonic Anhydrase]]''', Krishna Reddy Raghupathi
: '''[[User:Rami Rajasekhar Reddy|Molecular Playground/Avidin]]''', Rami Rajasekar Reddy
: '''[[Molecular Playground/Biotin binding avidin]]''', Diego Amado
: '''[[User:Jiaming Zhuang|Molecular Playground/MMP12]]''', Jiaming Zhuang
: ''' [[User:Jing Guo|Molecular Playground/Gluconase]]''', Jing Guo
: '''[[Molecular Playground/Glutathione Reductase]]''', Reuben Chacko

Thayumanavan & Vachet Labs

: '''[[Molecular Playground/Trypsin]]''', Gladys Murage

[http://people.chem.umass.edu/thompson/index.html Thompson Lab]

: '''[[Molecular Playground/Bacterial Chemotaxis Complex]]''', Elizabeth R. Haglin, Maryam Kashefi '''"Revised 2014"'''
: '''[[Molecular Playground/CheA]]''', Elizabeth R. Haglin
: '''[[Molecular Playground/Bacterial Chemotaxis Receptors]]''', Lynmarie K. Thompson, Shiela M. Jones
: '''[[Molecular Playground/Cytoplasmic domain of chemoreceptor of Thermotoga maritima]]''', Xuni Li

[http://www.chem.umass.edu/~vachet/index.html Vachet Lab]

: '''[[Molecular Playground/Human Serum Albumin]]''', Mahalia Serrano ''*Revised 2014*''
: '''[[Molecular playground/beta 2 microglobulin]]''', Nick Borotto, Tyler Marcinko ***'''Revised Fall 2014'''*** '''Best CBI Molecule Jmol scenes 2010'''
: '''[[Molecular Playground/Myoglobin]]''', Yuping Zhou
:'''[[Molecular Playground/ Copper-Zinc Superoxide Dismutase]]''', Shaynah Browne
: '''[[Molecular Playground/Ubiquitin salt bridge discussion]]''', Zhe Zhang

Vierling Lab

: '''[[Molecular Playground/sHSP]]''', Keith Ballard '''New 2014'''

Other Molecules of interest

: '''[[Molecular Playground/PcrA Helicase]]''', Luis E Ramirez-Tapia, [http://www.chem.umass.edu/~cmartin/ Martin Lab]

Other Laboratories

:'''[[Molecular Playground/4'-PHOSPHOPANTETHEINYL TRANSFERASE (Sfp)]]''', Jon Amoroso, Gitanjeli Prasad, Lawrence Sheringham Borketey, Schnarr lab
: '''[[6-deoxyerythronolide_B_synthase_(DEBS)|Molecular Playground/6-Deoxyerythronolide B Synthase]]''', Tsung-Yi Lin, Jon Amoroso, Lawrence Sheringham Borketey, Schnarr lab
: '''[[Molecular Playground/ACP apo]]''', Gitanjeli Prasad, Schnarr lab

: '''[[Molecular Playground/cytoplasmic domain of a serine chemotaxis receptor]]''', Meili Yang, Weis lab

: '''[[Molecular Playground/Alginate-Fall2011]]''', Joe White, David Griffi, Bhatia Lab
: '''[[Molecular Playground/Poly(ethylene glycol)]]''', Erika M. Saffer, Bhatia Lab

: '''[[Molecular Playground/YKL-40]]''', Ralph A. Francescone III, [http://www.bio.umass.edu/mcb/faculty/Shao.html Shao Lab]

: '''[[Molecular Playground/BLG|Molecular Playground/β-lactoglobulin]]''', Daniel Seeman, Dubin Lab

: '''[[Molecular Playground/ADAM13]]''', Genevieve Abbruzzese, Alfandari Lab

==Instructions==

'''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.'''

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.

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.

1. If you don't already have one, request a Proteopedia account and log in.

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.

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).

'''Complete the above steps before the CBI Molecule Workshop.'''

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.

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!

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).

==Links to HELP pages==
Overview at [[Help:Contents ]]

See also [[Help:Getting_Started_in_Proteopedia]]

Videos showing how to use Proteopedia:
[[Proteopedia:Video_Guide]]
(Sometimes slow -- if you pause the video and wait awhile it will download and then you can play it without interruptions)

[[Proteopedia:DIY:Scenes|Proteopedia Scenes: Do It Yourself]]
gives succinct step by step instructions on how to create a molecular scene.

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.
[http://www.proteopedia.org/wiki/images/1/1b/2009_07_13_Proteopedia_Workshop.pdf Proteopedia Workshop Slides]

[[Proteopedia:Guidelines for Ethical Writing]].
Please pay attention to the section about images. There are links to examples of images re-used with explicit permission.

For other help resources, click on [[Help:Contents|Help]] in the ''navigation'' box at the upper left of every page in Proteopedia.

User:Ololade Fatunmbi

2014-12-18T01:15:05Z

Ololade Fatunmbi:

* Full Real Name: Ololade Fatunmbi

* Position: Graduate Assistant Researcher

* Institution (NO ABBREVIATIONS): University of Massachusett

* City, State/Province, Country: Hadley, MA, USA

* Field of Expertise or Study: Bioinformatics and Mass Spectrometry

*[[Molecular Playground/Hemoglobin-Haptoglobin Complex]]

CBI Molecules

2014-12-18T01:11:15Z

Ololade Fatunmbi:

These are molecules under study by members of the [http://www.umass.edu/cbi/ University of Massachusetts Amherst Chemistry-Biology Interface Program].
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.

UMass CBI Members, add your molecules to the list (which is alphabetical by CBI research mentor); follow the instructions below the list.

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).
Follow the instructions at the bottom of this page.

==Molecules==
'''** Designates CBI Molecules Featured on [http://www.umass.edu/cbi/ CBI website]'''

[http://chamberslab.com/wp/ Chambers Lab]

: '''[[Molecular Playground/Glutamate Receptor]]''', Amanda Hussey, Steve McCarron, Rosie Combs-Bachmann, Mariel Feliciano

[http://www.chem.umass.edu/~chenlab/index.HTML Chen Lab]

: '''[[Molecular Playground/ClyA]]''', Monifa Fahie, Bib Yang '''Revised 2014'''
: '''[[Molecular Playground/OmpG]]''', Christina Chisholm, Monifa Fahie, Bib Yang '''Revised 2014'''

[http://openwetware.org/wiki/Chien Chien Lab]

: '''[[Molecular Playground/ClpP]]''', Lisa Hernandez, Rob Vass '''New 2014'''
: '''[[Molecular Playground/Homo-dimeric RcdA]]''', Kamal K. Joshi
: **'''[[Molecular Playground/Hexameric ClpX]]''', Joanne Lau '''Best CBI Molecule 2011'''
: '''[[Molecular Playground/DNA replication initiator DnaA]]''', Jing Liu

Farkas Lab
: '''[[Molecular Playground/CLOCK:BMAL1 heterodimer complex]]''', Hui-Hsien Lin, Joseph Hardie, Michael Mingroni '''New 2014'''

Forbes Lab

: '''[[Molecular Playground/CheR]]''', Miaomin Zhang
: '''[[Molecular Playground/RBP]]''', Jan Panteli
: '''[[Molecular Playground/TRAIL]]''', Charley Swofford

[http://www.biochem.umass.edu/garman/index.html Garman Lab]

: '''[[Molecular Playground/Human Protective Protein Cathepsin A]]''', Yadilette Rivera-Colon
: '''[[Molecular Playground/Human PPCA]]''', Nilima Kolli

[http://people.chem.umass.edu/gieraschlab/ Gierasch Lab]

: '''[[Molecular_Playground/DnaK]]''', Joseph Tilitsky, New 2014
: '''[[CRABP I ( Cellular Retinoic Acid Binding Protein )|Molecular Playground/CRABP I]]''', Kristine Faye Pobre, Mylene Ferrolino,Mangai Periasamy '''Best Overall CBI Molecule 2010'''
: '''[[Molecular Playground/CRABP I (Cellular Retinoic Acid Binding Protein)]]''', Gustavo Elberto Epalza Sanchez
: **'''[[Molecular_Playground/DHFR]]''', Karan Hingorani '''Best CBI Molecule 2012'''

[http://people.chem.umass.edu/jhardy/ Hardy Lab]

: '''[[Molecular Playground/Executioner Caspase-7]]''', Derek MacPherson, Maureen E. Hill
: '''[[Molecular Playground/Caspase-3 Regulatory Mechanisms]]''', Scott Eron, Bay Serrano, Yunlong Zhao
: '''[[Molecular Playground/Caspase-6 and neurodegeneration]]''', Kevin Buadlart Dagbay
: '''[[Molecular Playground/Caspase-7 Dynamics]]'''
: '''[[Molecular Playground/Caspase-9 Regulation]]''', Kristen Huber
: '''[[Molecular Playground/Caspase-6 (new)]]''', Elih Velazquez
: '''[[Molecular Playground/Influenza A M2 transmembrane domain]]''', Samantha Nicholls
: '''[[Molecular Playground/Dengue Virus Protease]]''', Muslum Yildiz

Hebert Lab

: '''[[Molecular_Playground/Hsp70-Hsp90]]''', Jill Graham "Revised 2014"
: '''[[Molecular_Playground/ERDj5]]''', Lydia Lamriben
: '''[[Molecular Playground/Saposin C]]''', Abla Tannous
: '''[[Molecular_Playground/ERMan1]]''', Johan Sunryd

[http://people.biochem.umass.edu/aheuck/aph.html Heuck Lab]

: '''[[Molecular_Playground/Pcr H]]''', Fabian Romano, Carolina Morell-Pérez, Yuzhou Tang

[http://people.chem.umass.edu/mholden/ Holden Lab]

: '''[[Molecular Playground/Protective Antigen]]''', Jing Huang

[http://www.chem.umass.edu/people/kaltashovlab/ Kaltashov Lab]
: '''[[Molecular Playground/Hb-Hp Complex]]''', Ololade Fatunmbi, Chibueze Egeruoh '''***New Fall 2014***'''
: '''[http://proteopedia.org/wiki/index.php/Chengfeng_Ren Molecular Playground/Inteferon]'''[Revised], Chengfeng Ren
: ''' [[Molecular Playground/Transferrin]]''', Khaja Muneeruddin, Jake Pawlowski
: '''[[Molecular Playground/Velaglucerase]]''', Adriana Kita
: '''[[Molecular Playground/Antithrombin-Heparin]]''', Yunlong Zhao

[http://people.chem.umass.edu/knapplab/?q=knappchem/index.html/ Knapp Lab]
: '''[[Molecular Playground/Prolyl Hydroxylase Domain (PHD) Enzyme]]''', Cristina Martin, Serap Pektas '''Best CBI Molecule Proteopedia Page 2010''' '''***New Fall 2014***'''
: '''[[Molecular Playground/FIH]]''', Vanessa Chaplin, Cornelius Taabazuing, Breanne Holmes, John Hangasky

[http://people.chem.umass.edu/mmaroney/ Maroney Lab]

: '''[[Molecular Playground/UreE]]''', Priyanka Basak, '''New 2014'''
: '''[[Molecular Playground/Nickel Superoxide Dismutase]]''', Carolyn Carr
: '''[[Molecular Playground/CsoR and RcnR]]''', Heidi Hu, Carolyn Carr, Hsin-Ting (Tiffany )Huang, '''Revised 2014'''
: '''[[Molecular Playground/HypA]]''', Heidi Hu

[http://www.chem.umass.edu/~cmartin/ Martin Lab]

: **'''[[Molecular Playground/T7 RNAP Conformations]]''', Luis E. Ramirez-Tapia '''Best CBI Molecule 2011'''
: '''[[Molecular Playground/T7 RNA Polymerase (7 mer int)]]''', Ankit Vahia
: '''[[Molecular Playground/Human mtRNA pol]]''', Ketan Mathavan

[http://www.peytonlab.org/ Peyton Lab]
: '''[[Molecular Playground/IntegrinBeta1]]''', Lauren Jansen, Lauren Barney, Elizabeth Brooks, Alyssa Schwartz ***'''NEW FALL 2014''''***
: '''[[Molecular Playground/MMP14]]''', Lauren Jansen
: '''[[Molecular Playground/C-Raf]]''', Thuy Nguyen
: '''[[Molecular Playground/FAK]]''', Dannielle Ryman

[http://roberts.openwetware.org/ Roberts Lab]

: '''[[Molecular Playground/Taxol]]''', Elizabeth Cummings, Rohan Patil, Sarah Wilson ***'''Revised Fall 2014'''***
: '''[[Molecular Playground/Insulin]]''', Whitney Stoppel

[http://www.umass.edu/rotellogroup/ Rotello Lab]

: '''[[Reverse transcriptase|Molecular Playground/Reverse Transcriptase]]''', Daniel Moyano-Marino
: '''[[Molecular Playground/Pancreatic Lipase]]''', Rui Tang
: '''[[Molecular playground/Chymotrypsin]]''', Brad
: '''[[Molecular Playground/Targeting Peptide]]''', David Solfiell

[http://http://www.umass.edu/schiffman/ Schiffman Lab]
: '''[[Molecular Playground/Streptavidin]]''', Katrina Rieger

[http://www.biochem.umass.edu/faculty/danny-j-schnell Schnell Lab]
: '''[[Molecular Playground/Tic40]]''', Mine Canakci

Tew Lab

: '''[[Molecular Playground/HIV Tat]]''', Brittany deRonde, Coralie Backlund

Thayumanavan Lab
: '''[[Interleukin-1 beta]]''', Huan He
: '''[[Molecular Playground/Lysozyme ]]''', Daniella Gonzalez
: '''[[Molecular Playground/Beta-galactosidase]]''', Judy Ventura
: '''[[User:Krishna Reddy Ragupathi|Molecular Playground/Carbonic Anhydrase]]''', Krishna Reddy Raghupathi
: '''[[User:Rami Rajasekhar Reddy|Molecular Playground/Avidin]]''', Rami Rajasekar Reddy
: '''[[Molecular Playground/Biotin binding avidin]]''', Diego Amado
: '''[[User:Jiaming Zhuang|Molecular Playground/MMP12]]''', Jiaming Zhuang
: ''' [[User:Jing Guo|Molecular Playground/Gluconase]]''', Jing Guo
: '''[[Molecular Playground/Glutathione Reductase]]''', Reuben Chacko

Thayumanavan & Vachet Labs

: '''[[Molecular Playground/Trypsin]]''', Gladys Murage

[http://people.chem.umass.edu/thompson/index.html Thompson Lab]

: '''[[Molecular Playground/Bacterial Chemotaxis Complex]]''', Elizabeth R. Haglin, Maryam Kashefi '''"Revised 2014"'''
: '''[[Molecular Playground/CheA]]''', Elizabeth R. Haglin
: '''[[Molecular Playground/Bacterial Chemotaxis Receptors]]''', Lynmarie K. Thompson, Shiela M. Jones
: '''[[Molecular Playground/Cytoplasmic domain of chemoreceptor of Thermotoga maritima]]''', Xuni Li

[http://www.chem.umass.edu/~vachet/index.html Vachet Lab]

: '''[[Molecular Playground/Human Serum Albumin]]''', Mahalia Serrano ''*Revised 2014*''
: '''[[Molecular playground/beta 2 microglobulin]]''', Nick Borotto, Tyler Marcinko ***'''Revised Fall 2014'''*** '''Best CBI Molecule Jmol scenes 2010'''
: '''[[Molecular Playground/Myoglobin]]''', Yuping Zhou
:'''[[Molecular Playground/ Copper-Zinc Superoxide Dismutase]]''', Shaynah Browne
: '''[[Molecular Playground/Ubiquitin salt bridge discussion]]''', Zhe Zhang

Vierling Lab

: '''[[Molecular Playground/sHSP]]''', Keith Ballard '''New 2014'''

Other Molecules of interest

: '''[[Molecular Playground/PcrA Helicase]]''', Luis E Ramirez-Tapia, [http://www.chem.umass.edu/~cmartin/ Martin Lab]

Other Laboratories

:'''[[Molecular Playground/4'-PHOSPHOPANTETHEINYL TRANSFERASE (Sfp)]]''', Jon Amoroso, Gitanjeli Prasad, Lawrence Sheringham Borketey, Schnarr lab
: '''[[6-deoxyerythronolide_B_synthase_(DEBS)|Molecular Playground/6-Deoxyerythronolide B Synthase]]''', Tsung-Yi Lin, Jon Amoroso, Lawrence Sheringham Borketey, Schnarr lab
: '''[[Molecular Playground/ACP apo]]''', Gitanjeli Prasad, Schnarr lab

: '''[[Molecular Playground/cytoplasmic domain of a serine chemotaxis receptor]]''', Meili Yang, Weis lab

: '''[[Molecular Playground/Alginate-Fall2011]]''', Joe White, David Griffi, Bhatia Lab
: '''[[Molecular Playground/Poly(ethylene glycol)]]''', Erika M. Saffer, Bhatia Lab

: '''[[Molecular Playground/YKL-40]]''', Ralph A. Francescone III, [http://www.bio.umass.edu/mcb/faculty/Shao.html Shao Lab]

: '''[[Molecular Playground/BLG|Molecular Playground/β-lactoglobulin]]''', Daniel Seeman, Dubin Lab

: '''[[Molecular Playground/ADAM13]]''', Genevieve Abbruzzese, Alfandari Lab

==Instructions==

'''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.'''

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.

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.

1. If you don't already have one, request a Proteopedia account and log in.

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.

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).

'''Complete the above steps before the CBI Molecule Workshop.'''

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.

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!

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).

==Links to HELP pages==
Overview at [[Help:Contents ]]

See also [[Help:Getting_Started_in_Proteopedia]]

Videos showing how to use Proteopedia:
[[Proteopedia:Video_Guide]]
(Sometimes slow -- if you pause the video and wait awhile it will download and then you can play it without interruptions)

[[Proteopedia:DIY:Scenes|Proteopedia Scenes: Do It Yourself]]
gives succinct step by step instructions on how to create a molecular scene.

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.
[http://www.proteopedia.org/wiki/images/1/1b/2009_07_13_Proteopedia_Workshop.pdf Proteopedia Workshop Slides]

[[Proteopedia:Guidelines for Ethical Writing]].
Please pay attention to the section about images. There are links to examples of images re-used with explicit permission.

For other help resources, click on [[Help:Contents|Help]] in the ''navigation'' box at the upper left of every page in Proteopedia.

Molecular Playground/Hb-Hp Complex

2014-12-18T01:07:29Z

Ololade Fatunmbi:

User:Ololade Fatunmbi

2014-12-18T01:06:53Z

Ololade Fatunmbi:

Molecular Playground/Hb-Hp Complex

2014-12-18T01:06:00Z

Ololade Fatunmbi:

[[Image:Newpathwayblackpng.png|thumb|400px|right| Figure 1. Hb-Hp/CD-163 Pathway during Intravascular hemolysis by Ololade Fatunmbi. Haptoglobin 1-1 (Hp), an abundant glycoprotein in blood binds free hemoglobin (Hb) dimers in one of the strongest non-covalent binding events known in biology. This interaction shields Hb residues that are prone to oxidative modification. Hb-Hp globin complexes bind to the CD163 cell surface receptor on macrophages leading to their internalization and catabolism. ]]

<table align="right" width="300" border="0" style="background-color:#e0e0e0;"><tr><td>
<Structure load=‘4f4o’ size='350' frame='true' align='right' caption='hhgyguygyugkuygkuyguyguygbhp’ scene='60/609783/Hbhpdimerblack/5'/>
</td></tr>
<tr><td>
<scene name='60/609783/Hbhpdimerblack/5'>Porcine Hemoglobin-Haptoglobin Complex </scene> <center>Color Code:</center>
<table border="2">
<tr>
<td>Haptoglobin (Hp) Magenta </td>
<td>Hemoglobin α-chain Cyan</td>
<td>Hemoglobin β-Chain Lime Green </td>
</tr>
<tr>
<td>Hp:<scene name='60/609783/Hbhpmonomer/13'> CD163 (HbHp receptor) recognition loop </scene>(silver)</td>
<td>Hb: <scene name='60/609783/Hbdimerfromhbhp/4'>Redox active residues</scene> (blue spheres)</td>
<td>HbHp complex: Residues involved in <scene name='60/609783/Hbhpmonomer/14'>salt bridges</scene> & <scene name='60/609783/Hbhpmonomer/16'>other electrostatic interactions</scene> (bold)</td>
</tr>
</table>

</td></tr></table>

==Summary==

[http://en.wikipedia.org/wiki/Hemoglobin ''Hemoglobin''] (Hb) is arguably one of the most studied proteins of all time. Hb is essential for our lives and nearly all other vertebrates because it transports oxygen from organs to tissues so that we can have energy. However, like most entities in life, too much of something may actually be harmful. In a process called [http://en.wikipedia.org/wiki/Hemolytic_anemia ''intravascular hemolysis''], high concentrations of Hb are released from red blood cells into the extracellular environment, which could cause [http://en.wikipedia.org/wiki/redox ''oxidative''] damage to our tissues [1]. [http://en.wikipedia.org/wiki/haptoglobin ''Haptoglobin''] (Hp), an [http://en.wikipedia.org/wiki/Acute-phase_protein ''acute phase'']glycoprotein, counteracts the negative physiological consequences of intravascular hemolysis by binding Hb [2-4] in one of strongest non-covalent events known in nature (Kd ~1 × 10–15 mol/L) [5,6]. See Figure 1.
==Function==
Hb physiologically exists as a <scene name='60/609783/Hbtetramer/2'>tetramer</scene> (Hbα1β1α2β2) found in red blood cells. During intravascular hemolysis, red blood cells (erythrocytes) rupture. Hb is then released into the [http://en.wikipedia.org/wiki/extracellular ''extracellular''] environment, and could be come very toxic to the body by causing severe oxidative tissue damage. Hb subunits dissociates into dimers (Hbα1β1) in the extracellular environment exposing <scene name='60/609783/Hbdimerfromhbhp/4'> residues that are prone to oxidative modification</scene> [10]. In addition, heme, the prosthetic group on Hb could react with hydrogen peroxide to generate reactive oxygen species (ROS) through Fenton and Haber-Weiss reactions and the iron present in heme catalyzes these reactions [3]. See Figure 2. Moreover, both the protein and heme regions of free Hb could cost excessive oxidative damage to the body by reacting with small molecules in circulation such as hydrogen peroxide. Extracellular Hb, could also react irreversibly with nitric oxide (NO), a critical regulator of smooth muscle tone and platelet activation [2]. The consumption of NO by Hb leads to limited bioavailability of NO and the production of nitrate and [http://en.wikipedia.org/wiki/methemoglobin ''methemoglobin''] [2].<scene name='60/609783/Hbhpmonomer/10'> Hp binding shields Hb </scene>and exposes an <scene name='60/609783/Hbhpmonomer/13'> neoepiptope</scene> recognized by the multifunctional receptor, CD163. The Hb-Hp complex binds CD-163 with high affinity and mediates haptoglobin-hemoglobin [http://en.wikipedia.org/wiki/endocytosis ''endocytosis''] and degradation [4].[[Image:Reaction.png |thumb|400px|right| Reactions of iron and hydrogen peroxide generate reactive oxygen species generated by [3]. Blue spheres indicate radicals.]]
<rb>Hp is found in nearly all mammals and some vertebrates. In humans, there are two allelic forms, Hp1 and Hp2, which manifest three phenotypes [2]. Hp1 is responsible for the Hp1-1 phenotype. Partial intragenic duplication in Hp1 gives rise to Hp2 allele, which is responsible for two phenotypes, Hp2-1 and Hp2-2 [1,2]. Both in vitro and in vivo studies have established that subjects with the Hp1-1 phenotype are more likely to resist cellular oxidative stress than those with the Hp2-2 phenotype, with Hp2-1 being intermediate [7].

== Structural Highlights ==
Haptoglobin 
The alone crystal structure of Hp has not yet been elucidated. Hp1-1 is ~90kda and exists as a <scene name='60/609783/Hpdimerblack/11'>heterodimer</scene> consisting of the two light chains and two heavy chains. The light chains are linked by the disulfide bond formed between <scene name='60/609783/Hpdimerblack/16'>Cys 33-Cys 33</scene>. Altogether there are 4 disulfides bonds on Hp and <scene name='60/609783/Hpdimerblack/15'>Cys 90 and Cys 207</scene> hold the light and heavy chains of Hp together. There are also <scene name='60/609783/Hpdimerblack/6'>4 n-linked glycosylation sites</scene> found on each monomer of Hp1-1 [8].
 
The light chain of Hp shares high homology with [http://en.wikipedia.org/wiki/Complement_control_protein ''complement control proteins''] while the heavy chain is very homologous with [http://en.wikipedia.org/wiki/serine_protease ''serine proteases''] [1]. Although Hp is not an active protease, the Hb-binding site in Hp is located in the region responsible for substrate specificity in other serine proteases (17). In serine proteases, the typical active-site residues are -histidine-57 and serine-195. In Hp these residues are replaced by lysine and alanine, respectively [9]). However, a substrate specific residue in trypsin (aspartic acid-189) does occur in Hp [9].

Hemoglobin-Haptoglobin Complex 
What makes the binding between Hp so tight and nearly irreversible? Recently, the crystal structure of porcine Hb-Hp was solved and revealed interactions involved in Hb-Hp interface [1]. Porcine Hp shares 82% homology with human Hp 1-1 [1,10]. The interaction between Hb and Hp is composed of various hydrophobic and <scene name='60/609783/Hbhpmonomer/14'>salt bridges</scene> and <scene name='60/609783/Hbhpmonomer/16'>other electrostatic interactions</scene> [10].

== Disease ==

Prevention of Renal Damage: Intravascular hemolysis occurs in several diseases including sickle-cell anemia and malaria [1]. Another consequence caused by free hemoglobin is oxidative damage in renal tissues following intravascular hemolysis [7]. Yet when haptoglobin binds to hemoglobin, the complex is too large to pass through the glomeruli of the kidney and will be removed via the reticuloendothelial system [7]. Therefore Hb induced injury to the parenchyma is prevented by haptoglobin [11]. 
 
Antibacterial Activity: When hemoglobin becomes non-covalently bound to haptoglobin, Hb and iron are no longer available to Escherichia coli and other bacteria that require iron [7]. Eaton was able to demonstrate that when Hp was given to rats that have been intraperitoneally injected with E. Coli and hemoglobin, Hp was able to prevent fatal effects [12].
 Antioxidant Activity: Haptoglobin has a significant role as an antioxidant [13]. Free hemoglobin also increases the peroxidation of purified arachidonic acid and other polyunsaturated fatty acids within neuronal cell membranes (10). Iron released from heme proteins can catalyze oxidative injury to neuronal cell membranes and might have a role in posttraumatic central nervous system (CNS) damage [14]. Haptoglobin, binds to Hb and removes it from the circulation and prevents iron-stimulated formation of oxygen radicals [15].

== Relevance ==

Hp has developed of a lot interest in drug therapy development recently because of its effectiveness in detoxifying free Hb activity when hemolytic related events occur in diseases [16-20] such as sickle cell anemia [16].

== Research Interests ==
Ololade Fatunmbi (Graduate Assistant Researcher) 
Studies of the Hp mediated Hb clearance pathway suggest that Hp may be used for targeted drug delivery (1). This use requires a detailed understanding of conformational dynamics and interactions in this protein/receptor system. However, Hb∙Hp/CD163 complex crystal structure and conformational dynamics have not yet been determined. I focus on studyingatomic level predictions of Hb-Hp/CD163 protein interactions and conformational dynamics using bioinformatics techniques and native mass spectrometry (MS).
 
Chibueze Egeruoh (Undergraduate Researcher) African trypanosomiasis or sleeping sickness is a parasitic disease of humans and other animals. On the structures of African trypanosomes, there is a coat of surface monolayer of variant surface glycoprotein (VSG) that protects the parasite. Within the VSG coat there are HbHp receptors that have the purposes of binding Hb-Hp acquisition heme through endocytosis so that the parasite would have nutrients such as iron present in Hb. Understanding the interaction of Hb-Hp complexes and trypanosome receptors will improve drug delivery to susceptible trypanosomes parasite. I conduct molecular modeling studies on trypanosome receptors and docking studies on Hb-Hp trypanosome receptors in complex with Hb-Hp complexes .

== References ==

<references/>

[http://www.ncbi.nlm.nih.gov/pubmed/11196644 1. Kristiansen M, Graversen JH, Jacobsen C, et al. Identification of the haemoglobin scavenger re- ceptor. Nature. 2001;409:198-201.] 
[http://www.ncbi.nlm.nih.gov/pubmed/19380867 2. Marianne Jensby Nielsen and Søren Kragh Moestrup. Receptor targeting of hemoglobin mediated by the haptoglobins: roles beyond heme scavenging. Blood. 2009. 114:764-771] 
[http://www.ncbi.nlm.nih.gov/pubmed/18486167 3. Isaac K. Quaye. Haptoglobin, inflammation and disease Trans R Soc Trop Med Hyg. 2008; 102, 735—742.] 
[http://www.ncbi.nlm.nih.gov/pubmed/20299103 4. Hanne Van Gorp, et al. Scavenger receptor CD-163, a Jack-of-all-trades and potential target for cell-directed therapy. Molecular Immunology. 2010; 47: 1650–1660.] 
[http://www.ncbi.nlm.nih.gov/pubmed/6751044 5. Bowman, BH, Kurosky, A: Haptoglobin: The evolutionary product of duplication, unequal crossing over, and point mutation. Adv Hum Genet 1982 12:189–261] 
[http://www.ncbi.nlm.nih.gov/pubmed/2073325 6. McCormick, DJ, Atassi, MZ: Hemoglobin binding with haptoglobin: Delineation of the haptoglobin binding site on the alpha-chain of human hemoglobin. J Protein Chem 1990 9:735–742] 
[http://www.ncbi.nlm.nih.gov/pubmed/15298155 7. S.M. Hossein Sadrzadeh, PhD, and Jafar Bozorgmehr, MD. Haptoglobin Phenotypes in Health and Disorders. Am J Clin Pathol. 2004; 121: 97-104] 
[http://www.ncbi.nlm.nih.gov/pubmed/172407 8. Black JA, Dixon GH. Amino-acid sequence of alpha chains of human haptoglobins. Nature. 1968;218:738-741.] 
[http://www.ncbi.nlm.nih.gov/pubmed/6997877 9. Alexander Kurosky et al. Covalent structure of human haptoglobin: A serine protease homolog. Biochemistry. 1980; 77: 3388-3392.] 
[http://www.ncbi.nlm.nih.gov/pubmed/22922649 10. Christian Brix Folsted Andersen. Structure of the haptoglobin–haemoglobin complex. Nature. 2012; 489: 456-459] 
[http://www.ncbi.nlm.nih.gov/pubmed/400530 11. Javid J. Human haptoglobins. Curr Top Hematol. 1978;1:151- 192.] 
[http://www.ncbi.nlm.nih.gov/pubmed/7036344 12. Eaton, et al. Haptoglobin: A natural bacteriostat. Science. 1982. 215: 691–693] 
[http://www.ncbi.nlm.nih.gov/pubmed/1476417 13. Lange V. Haptoglobin polymorphism: not only a genetic marker. Anthropol Anz. 1992;50:281-302.] 
[http://www.ncbi.nlm.nih.gov/pubmed/6094553 14. Sadrzadeh SMH, Graf E, Panter SS, et al. Hemoglobin: a biologic Fenton reagent. J Biol Chem. 1984;259:14354-14356 ] 
[http://www.ncbi.nlm.nih.gov/pubmed/8087243 15. Vercellotti GM, Balla G, Balla J, et al. Heme and the vasculature: an oxidative hazard that induces antioxidant defenses in the endothelium. Artif Cells Blood Substit Immobil Biotechnol. 1994;22:207-213.] 
[http://www.ncbi.nlm.nih.gov/pubmed/23140673 16. A. I. Alayash, C. B. Andersen, S. K. Moestrup, and L. Bülow. (2013) Haptoglobin: the hemoglobin detoxifier in plasma. Trends Biotechno,31. 2–3] 
[http://www.ncbi.nlm.nih.gov/pubmed/7865954 17. Gando S, Tedo I. (1994) The effects of massive transfusion and haptoglobin therapy on hemolysis in trauma patients. Surg Today. 9. 785-790.] 
[http://www.wiley.com/WileyCDA/WileyTitle/productCd-0470924314.html 18. Joseph Bertolini, Neil Goss, John Curling (2012) Production of Plasma Proteins for Therapeutic Use. Biochemistry; Edition 1: 332.] 
[http://www.ncbi.nlm.nih.gov/pubmed/8163802 19. Imaizumi H, Tsunoda K, Ichimiya N, Okamoto T, Namiki A. Repeated large-dose haptoglobin therapy in an extensively burned patient: case report. J Emerg Med 1994;12(1):33-37.] 
[http://www.ncbi.nlm.nih.gov/pubmed/23264591 20. D. J. Schaer, P. W. Buehler, A. I. Alayash, J. D. Belcher, and G. M. Vercellotti, Hemolysis and free hemoglobin revisited: exploring hemoglobin and hemin scavengers as a novel class of therapeutic proteins,” Blood, vol. 121, no. 8, pp. 1276–1284, 2013]

== Acknowledgements==
Ololade Fatunmbi and Chibueze Egeruoh 
PDB ID:4F4O from [http://www.rcsb.org/pdb/explore.do?structureId=4f4O Anderson, CB ''et. al'' (2012. Nature)]