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| | ==Crystal structure of the GAP-related domain of IQGAP1== | | ==Crystal structure of the GAP-related domain of IQGAP1== |
| - | <StructureSection load='3fay' size='340' side='right' caption='[[3fay]], [[Resolution|resolution]] 2.20Å' scene=''> | + | <StructureSection load='3fay' size='340' side='right'caption='[[3fay]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3fay]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FAY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3FAY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3fay]] 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=3FAY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FAY FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></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]] 2.2Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1wer|1wer]], [[1wq1|1wq1]], [[1nf1|1nf1]], [[3bxj|3bxj]]</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=3fay FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fay OCA], [https://pdbe.org/3fay PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fay RCSB], [https://www.ebi.ac.uk/pdbsum/3fay PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fay ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IQGAP1, KIAA0051 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3fay FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fay OCA], [http://pdbe.org/3fay PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fay RCSB], [http://www.ebi.ac.uk/pdbsum/3fay PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3fay ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/IQGA1_HUMAN IQGA1_HUMAN]] Binds to activated CDC42 but does not stimulate its GTPase activity. It associates with calmodulin. Could serve as an assembly scaffold for the organization of a multimolecular complex that would interface incoming signals to the reorganization of the actin cytoskeleton at the plasma membrane. May promote neurite outgrowth.<ref>PMID:15695813</ref> | + | [https://www.uniprot.org/uniprot/IQGA1_HUMAN IQGA1_HUMAN] Binds to activated CDC42 but does not stimulate its GTPase activity. It associates with calmodulin. Could serve as an assembly scaffold for the organization of a multimolecular complex that would interface incoming signals to the reorganization of the actin cytoskeleton at the plasma membrane. May promote neurite outgrowth.<ref>PMID:15695813</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Bellamy, H]] | + | [[Category: Large Structures]] |
| - | [[Category: Kurella, V B]] | + | [[Category: Bellamy H]] |
| - | [[Category: Parke, C L]] | + | [[Category: Kurella VB]] |
| - | [[Category: Richard, J M]] | + | [[Category: Parke CL]] |
| - | [[Category: Worthylake, D K]] | + | [[Category: Richard JM]] |
| - | [[Category: All alpha]] | + | [[Category: Worthylake DK]] |
| - | [[Category: Calmodulin-binding]]
| + | |
| - | [[Category: Cell membrane]]
| + | |
| - | [[Category: Membrane]]
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| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| Structural highlights
Function
IQGA1_HUMAN Binds to activated CDC42 but does not stimulate its GTPase activity. It associates with calmodulin. Could serve as an assembly scaffold for the organization of a multimolecular complex that would interface incoming signals to the reorganization of the actin cytoskeleton at the plasma membrane. May promote neurite outgrowth.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
IQGAP1 is a 190-kDa molecular scaffold containing several domains required for interaction with numerous proteins. One domain is homologous to Ras GTPase-activating protein (GAP) domains. However, instead of accelerating hydrolysis of bound GTP on Ras IQGAP1, using its GAP-related domain (GRD) binds to Cdc42 and Rac1 and stabilizes their GTP-bound states. We report here the crystal structure of the isolated IQGAP1 GRD. Despite low sequence conservation, the overall structure of the GRD is very similar to the GAP domains from p120 RasGAP, neurofibromin, and SynGAP. However, instead of the catalytic "arginine finger" seen in functional Ras GAPs, the GRD has a conserved threonine residue. GRD residues 1099-1129 have no structural equivalent in RasGAP and are seen to form an extension at one end of the molecule. Because the sequence of these residues is highly conserved, this region likely confers a functionality particular to IQGAP family GRDs. We have used isothermal titration calorimetry to demonstrate that the isolated GRD binds to active Cdc42. Assuming a mode of interaction similar to that displayed in the Ras-RasGAP complex, we created an energy-minimized model of Cdc42.GTP bound to the GRD. Residues of the GRD that contact Cdc42 map to the surface of the GRD that displays the highest level of sequence conservation. The model indicates that steric clash between threonine 1046 with the phosphate-binding loop and other subtle changes would likely disrupt the proper geometry required for GTP hydrolysis.
Crystal structure of the GTPase-activating protein-related domain from IQGAP1.,Kurella VB, Richard JM, Parke CL, Lecour LF Jr, Bellamy HD, Worthylake DK J Biol Chem. 2009 May 29;284(22):14857-65. Epub 2009 Mar 25. PMID:19321438[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Li Z, McNulty DE, Marler KJ, Lim L, Hall C, Annan RS, Sacks DB. IQGAP1 promotes neurite outgrowth in a phosphorylation-dependent manner. J Biol Chem. 2005 Apr 8;280(14):13871-8. Epub 2005 Jan 28. PMID:15695813 doi:http://dx.doi.org/M413482200
- ↑ Kurella VB, Richard JM, Parke CL, Lecour LF Jr, Bellamy HD, Worthylake DK. Crystal structure of the GTPase-activating protein-related domain from IQGAP1. J Biol Chem. 2009 May 29;284(22):14857-65. Epub 2009 Mar 25. PMID:19321438 doi:10.1074/jbc.M808974200
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