2ram: Difference between revisions

Latest revision as of 09:21, 21 February 2024

A NOVEL DNA RECOGNITION MODE BY NF-KB P65 HOMODIMER

Structural highlights

2ram is a 4 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.4Å
Ligands:	5IU, DTV
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TF65_MOUSE NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric p65-p50 and p65-c-Rel complexes are transcriptional activators. The NF-kappa-B p65-p65 complex appears to be involved in invasin-mediated activation of IL-8 expression (By similarity). The inhibitory effect of I-kappa-B upon NF-kappa-B the cytoplasm is exerted primarily through the interaction with p65. p65 shows a weak DNA-binding site which could contribute directly to DNA binding in the NF-kappa-B complex. Associates with chromatin at the NF-kappa-B promoter region via association with DDX1.^[1] ^[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

↑ Levy D, Kuo AJ, Chang Y, Schaefer U, Kitson C, Cheung P, Espejo A, Zee BM, Liu CL, Tangsombatvisit S, Tennen RI, Kuo AY, Tanjing S, Cheung R, Chua KF, Utz PJ, Shi X, Prinjha RK, Lee K, Garcia BA, Bedford MT, Tarakhovsky A, Cheng X, Gozani O. Lysine methylation of the NF-kappaB subunit RelA by SETD6 couples activity of the histone methyltransferase GLP at chromatin to tonic repression of NF-kappaB signaling. Nat Immunol. 2011 Jan;12(1):29-36. doi: 10.1038/ni.1968. Epub 2010 Dec 5. PMID:21131967 doi:10.1038/ni.1968
↑ Sen N, Paul BD, Gadalla MM, Mustafa AK, Sen T, Xu R, Kim S, Snyder SH. Hydrogen sulfide-linked sulfhydration of NF-kappaB mediates its antiapoptotic actions. Mol Cell. 2012 Jan 13;45(1):13-24. doi: 10.1016/j.molcel.2011.10.021. PMID:22244329 doi:10.1016/j.molcel.2011.10.021

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Levy D, Kuo AJ, Chang Y, Schaefer U, Kitson C, Cheung P, Espejo A, Zee BM, Liu CL, Tangsombatvisit S, Tennen RI, Kuo AY, Tanjing S, Cheung R, Chua KF, Utz PJ, Shi X, Prinjha RK, Lee K, Garcia BA, Bedford MT, Tarakhovsky A, Cheng X, Gozani O. Lysine methylation of the NF-kappaB subunit RelA by SETD6 couples activity of the histone methyltransferase GLP at chromatin to tonic repression of NF-kappaB signaling. Nat Immunol. 2011 Jan;12(1):29-36. doi: 10.1038/ni.1968. Epub 2010 Dec 5. PMID:21131967 doi:10.1038/ni.1968

[2] Sen N, Paul BD, Gadalla MM, Mustafa AK, Sen T, Xu R, Kim S, Snyder SH. Hydrogen sulfide-linked sulfhydration of NF-kappaB mediates its antiapoptotic actions. Mol Cell. 2012 Jan 13;45(1):13-24. doi: 10.1016/j.molcel.2011.10.021. PMID:22244329 doi:10.1016/j.molcel.2011.10.021

[1]

[2]

@@ Line 1: / Line 1: @@
-{{Seed}}
-[[Image:2ram.png|left|200px]]
-<!--
+==A NOVEL DNA RECOGNITION MODE BY NF-KB P65 HOMODIMER==
-The line below this paragraph, containing "STRUCTURE_2ram", creates the "Structure Box" on the page.
+<StructureSection load='2ram' size='340' side='right'caption='[[2ram]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[2ram]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RAM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RAM FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5IU:5-IODO-2-DEOXYURIDINE-5-MONOPHOSPHATE'>5IU</scene>, <scene name='pdbligand=DTV:(2S,3S)-1,4-DIMERCAPTOBUTANE-2,3-DIOL'>DTV</scene></td></tr>
-{{STRUCTURE_2ram|  PDB=2ram  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ram FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ram OCA], [https://pdbe.org/2ram PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ram RCSB], [https://www.ebi.ac.uk/pdbsum/2ram PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ram ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/TF65_MOUSE TF65_MOUSE] NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric p65-p50 and p65-c-Rel complexes are transcriptional activators. The NF-kappa-B p65-p65 complex appears to be involved in invasin-mediated activation of IL-8 expression (By similarity). The inhibitory effect of I-kappa-B upon NF-kappa-B the cytoplasm is exerted primarily through the interaction with p65. p65 shows a weak DNA-binding site which could contribute directly to DNA binding in the NF-kappa-B complex. Associates with chromatin at the NF-kappa-B promoter region via association with DDX1.<ref>PMID:21131967</ref> <ref>PMID:22244329</ref>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ra/2ram_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2ram ConSurf].
+<div style="clear:both"></div>
-===A NOVEL DNA RECOGNITION MODE BY NF-KB P65 HOMODIMER===
+==See Also==
+*[[NF-kB|NF-kB]]
+== References ==
-<!--
+<references/>
-The line below this paragraph, {{ABSTRACT_PUBMED_9437432}}, adds the Publication Abstract to the page
+__TOC__
-(as it appears on PubMed at http://www.pubmed.gov), where 9437432 is the PubMed ID number.
+</StructureSection>
--->
+[[Category: Large Structures]]
-{{ABSTRACT_PUBMED_9437432}}
-==About this Structure==
-RAM is a 4 chains structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RAM OCA].
-==Reference==
-<ref group="xtra">PMID:9437432</ref><references group="xtra"/>
 [[Category: Mus musculus]]
-[[Category: Chen, Y Q.]]
+[[Category: Chen YQ]]
-[[Category: Ghosh, G.]]
+[[Category: Ghosh G]]
-[[Category: Ghosh, S.]]
+[[Category: Ghosh S]]
-[[Category: Activator nuclear protein]]
-[[Category: Conformation]]
-[[Category: Dna-binding]]
-[[Category: Phosphorylation]]
-[[Category: Transcription regulation]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Feb 16 11:54:42 2009''

2ram: Difference between revisions

Latest revision as of 09:21, 21 February 2024

A NOVEL DNA RECOGNITION MODE BY NF-KB P65 HOMODIMER

Structural highlights

Function

Evolutionary Conservation

See Also

References

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