3TCA

Crystal structure of the Ras-associating and pleckstrin-homology domains of RIAM

Summary for 3TCA

• Entry DOI: 10.2210/pdb3tca/pdb
• Descriptor: Amyloid beta A4 precursor protein-binding family B member 1-interacting protein (2 entities in total)
• Functional Keywords: ra domain, rbd, ph domain, rap1-interacting adaptor molecule, integrin signaling, signaling protein
• Biological source: Mus musculus (mouse)
• Cellular location: Cell membrane; Peripheral membrane protein: Q8R5A3
• Total number of polymer chains: 2
• Total formula weight: 68652.84

Authors

Wu, J.,Hubbard, S.R. (deposition date: 2011-08-08, release date: 2012-09-26, Last modification date: 2023-09-13)

Primary citation

Wynne, J.P.,Wu, J.,Su, W.,Mor, A.,Patsoukis, N.,Boussiotis, V.A.,Hubbard, S.R.,Philips, M.R.
Rap1-interacting adapter molecule (RIAM) associates with the plasma membrane via a proximity detector.
J.Cell Biol., 199:317-329, 2012

PubMed Abstract: Adaptive immunity depends on lymphocyte adhesion that is mediated by the integrin lymphocyte functional antigen 1 (LFA-1). The small guanosine triphosphatase Rap1 regulates LFA-1 adhesiveness through one of its effectors, Rap1-interacting adapter molecule (RIAM). We show that RIAM was recruited to the lymphocyte plasma membrane (PM) through its Ras association (RA) and pleckstrin homology (PH) domains, both of which were required for lymphocyte adhesion. The N terminus of RIAM inhibited membrane translocation. In vitro, the RA domain bound both Rap1 and H-Ras with equal but relatively low affinity, whereas in vivo only Rap1 was required for PM association. The PH domain bound phosphoinositol 4,5-bisphosphate (PI(4,5)P(2)) and was responsible for the spatial distribution of RIAM only at the PM of activated T cells. We determined the crystal structure of the RA and PH domains and found that, despite an intervening linker of 50 aa, the two domains were integrated into a single structural unit, which was critical for proper localization to the PM. Thus, the RA-PH domains of RIAM function as a proximity detector for activated Rap1 and PI(4,5)P(2).

PubMed: 23045549
DOI: 10.1083/jcb.201201157

Experimental method

X-RAY DIFFRACTION (2.35 Å)