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2pz1

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[[Image:2pz1.jpg|left|200px]]<br /><applet load="2pz1" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2pz1, resolution 2.25&Aring;" />
 
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'''Crystal Structure of Auto-inhibited Asef'''<br />
 
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==Overview==
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==Crystal Structure of Auto-inhibited Asef==
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Autoinhibition of the Rho guanine nucleotide exchange factor ASEF is relieved by interaction with the APC tumor suppressor. Here we show that binding of the armadillo repeats of APC to a 'core APC-binding' (CAB) motif within ASEF, or truncation of the SH3 domain of ASEF, relieves autoinhibition, allowing the specific activation of CDC42. Structural determination of autoinhibited ASEF reveals that the SH3 domain forms an extensive interface with the catalytic DH and PH domains to obstruct binding and activation of CDC42, and the CAB motif is positioned adjacent to the SH3 domain to facilitate activation by APC. In colorectal cancer cell lines, full-length, but not truncated, APC activates CDC42 in an ASEF-dependent manner to suppress anchorage-independent growth. We therefore propose a model in which ASEF acts as a tumor suppressor when activated by APC and inactivation of ASEF by mutation or APC truncation promotes tumorigenesis.
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<StructureSection load='2pz1' size='340' side='right'caption='[[2pz1]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2pz1]] is a 1 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=2PZ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PZ1 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]] 2.25&#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=2pz1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pz1 OCA], [https://pdbe.org/2pz1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pz1 RCSB], [https://www.ebi.ac.uk/pdbsum/2pz1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pz1 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/ARHG4_HUMAN ARHG4_HUMAN] Acts as guanine nucleotide exchange factor (GEF) for RHOA, RAC1 and CDC42 GTPases. Binding of APC may activate RAC1 GEF activity. The APC-ARHGEF4 complex seems to be involved in cell migration as well as in E-cadherin-mediated cell-cell adhesion. Required for MMP9 up-regulation via the JNK signaling pathway in colorectal tumor cells. Involved in tumor angiogenesis and may play a role in intestinal adenoma formation and tumor progression.<ref>PMID:10947987</ref> <ref>PMID:12598901</ref> <ref>PMID:17145773</ref> <ref>PMID:17599059</ref> <ref>PMID:19893577</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/pz/2pz1_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=2pz1 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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2PZ1 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence 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=2PZ1 OCA].
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*[[Rho guanine nucleotide exchange factor 3D structures|Rho guanine nucleotide exchange factor 3D structures]]
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== References ==
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==Reference==
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<references/>
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Release of autoinhibition of ASEF by APC leads to CDC42 activation and tumor suppression., Mitin N, Betts L, Yohe ME, Der CJ, Sondek J, Rossman KL, Nat Struct Mol Biol. 2007 Sep;14(9):814-23. Epub 2007 Aug 19. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17704816 17704816]
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Betts, L.]]
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[[Category: Betts L]]
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[[Category: Rossman, K L.]]
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[[Category: Rossman KL]]
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[[Category: Sondek, J.]]
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[[Category: Sondek J]]
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[[Category: beta barrel]]
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[[Category: beta sandwich]]
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[[Category: helical bundle]]
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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 18:34:27 2008''
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Current revision

Crystal Structure of Auto-inhibited Asef

PDB ID 2pz1

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