2aze

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(New page: 200px<br /> <applet load="2aze" size="450" color="white" frame="true" align="right" spinBox="true" caption="2aze, resolution 2.55&Aring;" /> '''Structure of the Rb...)
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[[Image:2aze.gif|left|200px]]<br />
 
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<applet load="2aze" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2aze, resolution 2.55&Aring;" />
 
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'''Structure of the Rb C-terminal domain bound to an E2F1-DP1 heterodimer'''<br />
 
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==Overview==
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==Structure of the Rb C-terminal domain bound to an E2F1-DP1 heterodimer==
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The retinoblastoma (Rb) protein negatively regulates the G1-S transition, by binding to the E2F transcription factors, until cyclin-dependent, kinases phosphorylate Rb, causing E2F release. The Rb pocket domain is, necessary for E2F binding, but the Rb C-terminal domain (RbC) is also, required for growth suppression. Here we demonstrate a high-affinity, interaction between RbC and E2F-DP heterodimers shared by all Rb and E2F, family members. The crystal structure of an RbC-E2F1-DP1 complex reveals, an intertwined heterodimer in which the marked box domains of both E2F1, and DP1 contact RbC. We also demonstrate that phosphorylation of RbC at, serines 788 and 795 destabilizes one set of RbC-E2F-DP interactions, directly, while phosphorylation at threonines 821 and 826 induces an, intramolecular interaction between RbC and the Rb pocket that destabilizes, the remaining interactions indirectly. Our findings explain the, requirement of RbC for high-affinity E2F binding and growth suppression, and establish a mechanism for the regulation of Rb-E2F association by, phosphorylation.
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<StructureSection load='2aze' size='340' side='right'caption='[[2aze]], [[Resolution|resolution]] 2.55&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2aze]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AZE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AZE FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.55&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2aze FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aze OCA], [https://pdbe.org/2aze PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2aze RCSB], [https://www.ebi.ac.uk/pdbsum/2aze PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2aze ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/TFDP1_HUMAN TFDP1_HUMAN] Can stimulate E2F-dependent transcription. Binds DNA cooperatively with E2F family members through the E2 recognition site, 5'-TTTC[CG]CGC-3', found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication. The E2F1:DP complex appears to mediate both cell proliferation and apoptosis. Blocks adipocyte differentiation by repressing CEBPA binding to its target gene promoters (PubMed:20176812).<ref>PMID:20176812</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/az/2aze_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2aze ConSurf].
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<div style="clear:both"></div>
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==Disease==
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==See Also==
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Known diseases associated with this structure: Bladder cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=180200 180200]], Osteosarcoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=180200 180200]], Pinealoma with bilateral retinoblastoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=180200 180200]], Retinoblastoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=180200 180200]]
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*[[Retinoblastoma protein|Retinoblastoma protein]]
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== References ==
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==About this Structure==
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<references/>
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2AZE is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2AZE OCA].
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__TOC__
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</StructureSection>
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==Reference==
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Structure of the Rb C-terminal domain bound to E2F1-DP1: a mechanism for phosphorylation-induced E2F release., Rubin SM, Gall AL, Zheng N, Pavletich NP, Cell. 2005 Dec 16;123(6):1093-106. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16360038 16360038]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Gall, A.L.]]
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[[Category: Gall AL]]
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[[Category: Pavletich, N.P.]]
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[[Category: Pavletich NP]]
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[[Category: Rubin, S.M.]]
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[[Category: Rubin SM]]
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[[Category: Zheng, N.]]
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[[Category: Zheng N]]
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[[Category: beta sandwich]]
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[[Category: coiled coil]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:56:27 2007''
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Current revision

Structure of the Rb C-terminal domain bound to an E2F1-DP1 heterodimer

PDB ID 2aze

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