|
|
| (2 intermediate revisions by the same user not shown) |
| Line 1: |
Line 1: |
| | |
| ==Crystal structure of the atypical phosphoinositide (aPI) binding domain of IQGAP2== | | ==Crystal structure of the atypical phosphoinositide (aPI) binding domain of IQGAP2== |
| <StructureSection load='4eza' size='340' side='right' caption='[[4eza]], [[Resolution|resolution]] 1.50Å' scene=''> | | <StructureSection load='4eza' size='340' side='right'caption='[[4eza]], [[Resolution|resolution]] 1.50Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[4eza]] is a 2 chain structure with 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=4EZA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EZA FirstGlance]. <br> | | <table><tr><td colspan='2'>[[4eza]] 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=4EZA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EZA FirstGlance]. <br> |
| </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IQGAP2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5Å</td></tr> |
| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4eza FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eza OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4eza RCSB], [http://www.ebi.ac.uk/pdbsum/4eza PDBsum]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4eza FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eza OCA], [https://pdbe.org/4eza PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4eza RCSB], [https://www.ebi.ac.uk/pdbsum/4eza PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4eza ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/IQGA2_HUMAN IQGA2_HUMAN]] Binds to activated CDC42 and RAC1 but does not seem to stimulate their GTPase activity. Associates with calmodulin. | | [https://www.uniprot.org/uniprot/IQGA2_HUMAN IQGA2_HUMAN] Binds to activated CDC42 and RAC1 but does not seem to stimulate their GTPase activity. Associates with calmodulin. |
| <div style="background-color:#fffaf0;">
| |
| == Publication Abstract from PubMed ==
| |
| Class I phosphoinositide (PI) 3-kinases act through effector proteins whose 3-PI selectivity is mediated by a limited repertoire of structurally defined, lipid recognition domains. We describe here the lipid preferences and crystal structure of a new class of PI binding module exemplified by select IQGAPs (IQ motif containing GTPase activating proteins) known to co-ordinate cellular signalling events and cytoskeletal dynamics. This module is defined by a C-terminal 105-107 amino acid region of which that from IQGAP1 and 2, but not IQGAP3, binds preferentially to phosphatidylinositol 3,4,5-trisphosphate (PtdInsP(3)). The binding affinity for PtdInsP(3), together with other, secondary target-recognition characteristics, are comparable to those of the pleckstrin homology (PH) domain of cytohesin-3 (general receptor for phosphoinositides 1), an established PtdInsP(3) effector protein. Importantly, the IQGAP1 C-terminal domain and the cytohesin-3 PH domain, each tagged with enhanced green fluorescent protein, both re-localized from the cytosol to the cell periphery following the activation of PI 3-kinase in Swiss 3T3 fibroblasts, consistent with their common, selective recognition of endogenous 3-PI(s). The crystal structure of the C-terminal IQGAP2 PI binding module reveals unexpected topological similarity to an integral fold of C2 domains, including a putative basic binding pocket. We propose that this module integrates select IQGAP proteins with PI 3-kinase signalling and constitutes a novel, atypical phosphoinositide (aPI) binding domain that may represent the first of a larger group, each perhaps structurally unique but collectively dissimilar from the known PI recognition modules.
| |
| | |
| IQGAP proteins reveal an atypical phosphoinositide (aPI) binding domain with a pseudo C2 domain fold.,Dixon MJ, Gray A, Schenning M, Agacan M, Tempel W, Tong Y, Nedyalkova L, Park HW, Leslie NR, van Aalten DM, Downes CP, Batty IH J Biol Chem. 2012 Apr 5. PMID:22493426<ref>PMID:22493426</ref>
| |
| | |
| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| |
| </div>
| |
| == References ==
| |
| <references/>
| |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| [[Category: Aalten, D M.F Van]] | | [[Category: Large Structures]] |
| [[Category: Agacan, M]] | | [[Category: Agacan M]] |
| [[Category: Arrowsmith, C H]] | | [[Category: Arrowsmith CH]] |
| [[Category: Batty, I H]] | | [[Category: Batty IH]] |
| [[Category: Bochkarev, A]] | | [[Category: Bochkarev A]] |
| [[Category: Bountra, C]] | | [[Category: Bountra C]] |
| [[Category: Crombet, L]] | | [[Category: Crombet L]] |
| [[Category: Dixon, M J]] | | [[Category: Dixon MJ]] |
| [[Category: Downes, C P]] | | [[Category: Downes CP]] |
| [[Category: Edwards, A M]] | | [[Category: Edwards AM]] |
| [[Category: Gray, A]] | | [[Category: Gray A]] |
| [[Category: Leslie, N R]] | | [[Category: Leslie NR]] |
| [[Category: Nedyalkova, L]] | | [[Category: Nedyalkova L]] |
| [[Category: Park, H]] | | [[Category: Park H]] |
| [[Category: Structural genomic]]
| | [[Category: Schenning M]] |
| [[Category: Schenning, M]] | | [[Category: Tempel W]] |
| [[Category: Tempel, W]] | | [[Category: Tong Y]] |
| [[Category: Tong, Y]] | | [[Category: Van Aalten DMF]] |
| [[Category: Weigelt, J]] | | [[Category: Weigelt J]] |
| [[Category: Zhong, N]] | | [[Category: Zhong N]] |
| [[Category: Gap]] | |
| [[Category: Sgc]]
| |
| [[Category: Signaling protein]]
| |