6e31: Difference between revisions
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The | ==Crystal structure of RIAM in an autoinhibited configuration.== | ||
<StructureSection load='6e31' size='340' side='right'caption='[[6e31]], [[Resolution|resolution]] 2.40Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6e31]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E31 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6E31 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</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=6e31 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e31 OCA], [https://pdbe.org/6e31 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6e31 RCSB], [https://www.ebi.ac.uk/pdbsum/6e31 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6e31 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/B1AYC9_MOUSE B1AYC9_MOUSE] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
RAP1-interacting adapter molecule (RIAM) mediates RAP1-induced integrin activation. The RAS-association (RA) segment of the RA-PH module of RIAM interacts with GTP-bound RAP1 and phosphoinositol 4,5 bisphosphate but this interaction is inhibited by the N-terminal segment of RIAM. Here we report the structural basis for the autoinhibition of RIAM by an intramolecular interaction between the IN region (aa 27-93) and the RA-PH module. We solved the crystal structure of IN-RA-PH to a resolution of 2.4-A. The structure reveals that the IN segment associates with the RA segment and thereby suppresses RIAM:RAP1 association. This autoinhibitory configuration of RIAM can be released by phosphorylation at Tyr45 in the IN segment. Specific inhibitors of focal adhesion kinase (FAK) blocked phosphorylation of Tyr45, inhibited stimulated translocation of RIAM to the plasma membrane, and inhibited integrin-mediated cell adhesion in a Tyr45-dependent fashion. Our results reveal an unusual regulatory mechanism in small GTPase signaling by which the effector molecule is autoinhibited for GTPase interaction, and a modality of integrin activation at the level of RIAM through a FAK-mediated feedforward mechanism that involves reversal of autoinhibition by a tyrosine kinase associated with integrin signaling. | |||
Molecular basis for autoinhibition of RIAM regulated by FAK in integrin activation.,Chang YC, Su W, Cho EA, Zhang H, Huang Q, Philips MR, Wu J Proc Natl Acad Sci U S A. 2019 Feb 7. pii: 1818880116. doi:, 10.1073/pnas.1818880116. PMID:30733287<ref>PMID:30733287</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6e31" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: Huang | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Mus musculus]] | |||
[[Category: Chang YC]] | |||
[[Category: Huang Q]] | |||
[[Category: Philips MR]] | |||
[[Category: Su W]] | |||
[[Category: Wu J]] | |||
[[Category: Zhang H]] | |||
Latest revision as of 09:17, 11 October 2023
Crystal structure of RIAM in an autoinhibited configuration.Crystal structure of RIAM in an autoinhibited configuration.
Structural highlights
FunctionPublication Abstract from PubMedRAP1-interacting adapter molecule (RIAM) mediates RAP1-induced integrin activation. The RAS-association (RA) segment of the RA-PH module of RIAM interacts with GTP-bound RAP1 and phosphoinositol 4,5 bisphosphate but this interaction is inhibited by the N-terminal segment of RIAM. Here we report the structural basis for the autoinhibition of RIAM by an intramolecular interaction between the IN region (aa 27-93) and the RA-PH module. We solved the crystal structure of IN-RA-PH to a resolution of 2.4-A. The structure reveals that the IN segment associates with the RA segment and thereby suppresses RIAM:RAP1 association. This autoinhibitory configuration of RIAM can be released by phosphorylation at Tyr45 in the IN segment. Specific inhibitors of focal adhesion kinase (FAK) blocked phosphorylation of Tyr45, inhibited stimulated translocation of RIAM to the plasma membrane, and inhibited integrin-mediated cell adhesion in a Tyr45-dependent fashion. Our results reveal an unusual regulatory mechanism in small GTPase signaling by which the effector molecule is autoinhibited for GTPase interaction, and a modality of integrin activation at the level of RIAM through a FAK-mediated feedforward mechanism that involves reversal of autoinhibition by a tyrosine kinase associated with integrin signaling. Molecular basis for autoinhibition of RIAM regulated by FAK in integrin activation.,Chang YC, Su W, Cho EA, Zhang H, Huang Q, Philips MR, Wu J Proc Natl Acad Sci U S A. 2019 Feb 7. pii: 1818880116. doi:, 10.1073/pnas.1818880116. PMID:30733287[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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