4b93
From Proteopedia
Complex of Vamp7 cytoplasmic domain with 2nd ankyrin repeat domain of Varp
Structural highlights
Function[VAMP7_MOUSE] Involved in the targeting and/or fusion of transport vesicles to their target membrane during transport of proteins from the early endosome to the lysosome. Required for heterotypic fusion of late endosomes with lysosomes and homotypic lysosomal fusion. Required for calcium regulated lysosomal exocytosis. Involved in the export of chylomicrons from the endoplasmic reticulum to the cis Golgi. Required for exocytosis of mediators during eosinophil and neutrophil degranulation, and target cell killing by natural killer cells. Required for focal exocytosis of late endocytic vesicles during phagosome formation.[1] [ANR27_HUMAN] May be a Rab21 guanine exchange factor and regulate endosome dynamics (By similarity). Publication Abstract from PubMedSNAREs provide energy and specificity to membrane fusion events. Fusogenic trans-SNARE complexes are assembled from glutamine-contributing SNAREs (Q-SNAREs) embedded in one membrane and an arginine-contributing SNARE (R-SNARE) embedded in the other. Regulation of membrane fusion events is crucial for intracellular trafficking. We identify the endosomal protein Varp as an R-SNARE-binding regulator of SNARE complex formation. Varp colocalizes with and binds to VAMP7, an R-SNARE that is involved in both endocytic and secretory pathways. We present the structure of the second ankyrin repeat domain of mammalian Varp in complex with the cytosolic portion of VAMP7. The VAMP7-SNARE motif is trapped between Varp and the VAMP7 longin domain, and hence Varp kinetically inhibits the ability of VAMP7 to form SNARE complexes. This inhibition will be increased when Varp can also bind to other proteins present on the same membrane as VAMP7, such as Rab32-GTP. The binding of Varp to VAMP7 traps VAMP7 in a closed, fusogenically inactive conformation.,Schafer IB, Hesketh GG, Bright NA, Gray SR, Pryor PR, Evans PR, Luzio JP, Owen DJ Nat Struct Mol Biol. 2012 Dec;19(12):1300-9. doi: 10.1038/nsmb.2414. Epub 2012, Oct 28. PMID:23104059[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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