6OLU
RIAM RA-PH core structure in the P212121 space group
Summary for 6OLU
| Entry DOI | 10.2210/pdb6olu/pdb |
| Descriptor | Amyloid beta A4 precursor protein-binding family B member 1-interacting protein (2 entities in total) |
| Functional Keywords | rap1 effector ra-ph, signaling protein |
| Biological source | Mus musculus (Mouse) |
| Total number of polymer chains | 1 |
| Total formula weight | 31053.58 |
| Authors | |
| Primary citation | Cho, E.A.,Zhang, P.,Kumar, V.,Kavalchuk, M.,Zhang, H.,Huang, Q.,Duncan, J.S.,Wu, J. Phosphorylation of RIAM by src promotes integrin activation by unmasking the PH domain of RIAM. Structure, 29:320-, 2021 Cited by PubMed Abstract: Integrin activation controls cell adhesion, migration, invasion, and extracellular matrix remodeling. RIAM (RAP1-GTP-interacting adaptor molecule) is recruited by activated RAP1 to the plasma membrane (PM) to mediate integrin activation via an inside-out signaling pathway. This process requires the association of the pleckstrin homology (PH) domain of RIAM with the membrane PIP2. We identify a conserved intermolecular interface that masks the PIP2-binding site in the PH domains of RIAM. Our data indicate that phosphorylation of RIAM by Src family kinases disrupts this PH-mediated interface, unmasks the membrane PIP2-binding site, and promotes integrin activation. We further demonstrate that this process requires phosphorylation of Tyr267 and Tyr427 in the RIAM PH domain by Src. Our data reveal an unorthodox regulatory mechanism of small GTPase effector proteins by phosphorylation-dependent PM association of the PH domain and provide new insights into the link between Src kinases and integrin signaling. PubMed: 33275877DOI: 10.1016/j.str.2020.11.011 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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