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2j6o

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[[Image:2j6o.gif|left|200px]]<br /><applet load="2j6o" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2j6o, resolution 2.225&Aring;" />
 
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'''ATYPICAL POLYPROLINE RECOGNITION BY THE CMS N-TERMINAL SH3 DOMAIN. CMS:CD2 HETEROTRIMER'''<br />
 
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==Overview==
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==ATYPICAL POLYPROLINE RECOGNITION BY THE CMS N-TERMINAL SH3 DOMAIN. CMS:CD2 HETEROTRIMER==
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The CIN85/CMS (human homologs of mouse SH3KBP1/CD2AP) family of endocytic adaptor proteins has the ability to engage multiple effectors and couple cargo trafficking with the cytoskeleton. CIN85 and CMS (Cas ligand with multiple Src homology 3 (SH3) domains) facilitate the formation of large multiprotein complexes required for an efficient internalization of cell surface receptors. It has recently been shown that c-Cbl/Cbl-b could mediate the formation of a ternary complex between one c-Cbl/Cbl-b molecule and two SH3 domains of CIN85, important for the ability of Cbl to promote epidermal growth factor receptor down-regulation. To further investigate whether multimerization is conserved within the family of adaptor proteins, we have solved the crystal structures of the CMS N-terminal SH3 domain-forming complexes with Cbl-b- and CD2-derived peptides. Together with biochemical evidence, the structures support the notion that, despite clear differences in the interaction surface, both Cbl-b and CD2 can mediate multimerization of N-terminal CMS SH3 domains. Detailed analyses on the interacting surfaces also provide the basis for a differential Cbl-b molecular recognition of CMS and CIN85.
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<StructureSection load='2j6o' size='340' side='right'caption='[[2j6o]], [[Resolution|resolution]] 2.23&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2j6o]] is a 2 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=2J6O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2J6O 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]] 2.23&#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=2j6o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j6o OCA], [https://pdbe.org/2j6o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2j6o RCSB], [https://www.ebi.ac.uk/pdbsum/2j6o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2j6o ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/CD2AP_HUMAN CD2AP_HUMAN] Defects in CD2AP are the cause of susceptibility to focal segmental glomerulosclerosis type 3 (FSGS3) [MIM:[https://omim.org/entry/607832 607832]. A renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and edema. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state requiring either dialysis therapy or kidney transplantation.<ref>PMID:12764198</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/CD2AP_HUMAN CD2AP_HUMAN] Seems to act as an adapter protein between membrane proteins and the actin cytoskeleton. May play a role in receptor clustering and cytoskeletal polarity in the junction between T-cell and antigen-presenting cell. May anchor the podocyte slit diaphragm to the actin cytoskeleton in renal glomerolus. Also required for cytokinesis.<ref>PMID:15800069</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/j6/2j6o_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=2j6o ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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2J6O 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://oca.weizmann.ac.il/oca-bin/ocashort?id=2J6O OCA].
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*[[CD2-associated protein|CD2-associated protein]]
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*[[CD2-associated protein 3D structures|CD2-associated protein 3D structures]]
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==Reference==
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== References ==
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Atypical polyproline recognition by the CMS N-terminal Src homology 3 domain., Moncalian G, Cardenes N, Deribe YL, Spinola-Amilibia M, Dikic I, Bravo J, J Biol Chem. 2006 Dec 15;281(50):38845-53. Epub 2006 Oct 3. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17020880 17020880]
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<references/>
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__TOC__
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</StructureSection>
[[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: Bravo, J.]]
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[[Category: Bravo J]]
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[[Category: Cardenes, N.]]
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[[Category: Cardenes N]]
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[[Category: Deribe, Y L.]]
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[[Category: Deribe YL]]
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[[Category: Dikic, I.]]
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[[Category: Dikic I]]
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[[Category: Moncalian, G.]]
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[[Category: Moncalian G]]
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[[Category: Spinola-Amilibia, M.]]
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[[Category: Spinola-Amilibia M]]
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[[Category: adaptor protein]]
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[[Category: cms]]
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[[Category: coiled coil]]
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[[Category: egfr downregulation]]
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[[Category: phosphorylation]]
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[[Category: protein binding]]
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[[Category: sh3 domain]]
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[[Category: sh3 domain recognition]]
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[[Category: sh3-binding]]
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[[Category: signaling protein]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:59:47 2008''
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Current revision

ATYPICAL POLYPROLINE RECOGNITION BY THE CMS N-TERMINAL SH3 DOMAIN. CMS:CD2 HETEROTRIMER

PDB ID 2j6o

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