3bc1
From Proteopedia
Crystal Structure of the complex Rab27a-Slp2a
Structural highlights
Function[RB27A_MOUSE] Plays a role in cytotoxic granule exocytosis in lymphocytes. Required for both granule maturation and granule docking and priming at the immunologic synapse (By similarity). [SYTL2_HUMAN] Isoform 1 acts as a RAB27A effector protein and plays a role in cytotoxic granule exocytosis in lymphocytes. It is required for cytotoxic granule docking at the immunologic synapse. Isoform 4 binds phosphatidylserine (PS) and phosphatidylinositol-4,5-bisphosphate (PIP2) and promotes the recruitment of glucagon-containing granules to the cell membrane in pancreatic alpha cells. Binding to PS is inhibited by Ca(2+) while binding to PIP2 is Ca(2+) insensitive.[1] [2] [3] 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 PubMedRab GTPases coordinate vesicular trafficking within eukaryotic cells by collaborating with a set of effector proteins. Rab27a regulates numerous exocytotic pathways, and its dysfunction causes the Griscelli syndrome human immunodeficiency. Exophilin4/Slp2-a localizes on phosphatidylserine-enriched plasma membrane, and its N-terminal Rab27-binding domain (RBD27) specifically recognizes Rab27 on the surfaces of melanosomes and secretory granules prior to docking and fusion. To characterize the selective binding of Rab27 to 11 various effectors, we have determined the 1.8 A resolution structure of Rab27a in complex with Exophilin4 RBD27. The effector packs against the switch and interswitch elements of Rab27a, and specific affinity toward Rab27a is modulated by a shift in the orientation of the effector structural motif (S/T)(G/L)xW(F/Y)(2). The observed structural complementation between the interacting surfaces of Rab27a and Exophilin4 sheds light on the disparities among the Rab27 effectors and outlines a general mechanism for their recruitment. Elucidation of Rab27 recruitment by its effectors: structure of Rab27a bound to Exophilin4/Slp2-a.,Chavas LM, Ihara K, Kawasaki M, Torii S, Uejima T, Kato R, Izumi T, Wakatsuki S Structure. 2008 Oct 8;16(10):1468-77. PMID:18940603[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Lk3 transgenic mice | Small monomeric GTPase | Chavas, L M.G | Ihara, K | Kawasaki, M | Wakatsuki, S | Exophilin-4 | Gdpnp | Gtp-binding | Gtpase | Lipoprotein | Membrane | Methylation | Nucleotide-binding | Prenylation | Rab | Rab27 | Signaling protein | Signaling protein-transport protein complex | Slp2a
