5low | pdb_00005low
Structure of the Ca2+-bound Rabphilin 3A C2B domain SNAP25 complex (P21 space group)
Structural highlights
FunctionRP3A_RAT Protein transport. Probably involved with Ras-related protein Rab-3A in synaptic vesicle traffic and/or synaptic vesicle fusion. Could play a role in neurotransmitter release by regulating membrane flow in the nerve terminal. Publication Abstract from PubMedMembrane fusion is essential in a myriad of eukaryotic cell biological processes, including the synaptic transmission. Rabphilin-3A is a membrane trafficking protein involved in the calcium-dependent regulation of secretory vesicle exocytosis in neurons and neuroendocrine cells, but the underlying mechanism remains poorly understood. Here, we report the crystal structures and biochemical analyses of Rabphilin-3A C2B-SNAP25 and C2B-phosphatidylinositol 4,5-bisphosphate (PIP2) complexes, revealing how Rabphilin-3A C2 domains operate in cooperation with PIP2/Ca(2+) and SNAP25 to bind the plasma membrane, adopting a conformation compatible to interact with the complete SNARE complex. Comparisons with the synaptotagmin1-SNARE show that both proteins contact the same SNAP25 surface, but Rabphilin-3A uses a unique structural element. Data obtained here suggest a model to explain the Ca(2+)-dependent fusion process by membrane bending with a myriad of variations depending on the properties of the C2 domain-bearing protein, shedding light to understand the fine-tuning control of the different vesicle fusion events. Structural characterization of the Rabphilin-3A-SNAP25 interaction.,Ferrer-Orta C, Perez-Sanchez MD, Coronado-Parra T, Silva C, Lopez-Martinez D, Baltanas-Copado J, Gomez-Fernandez JC, Corbalan-Garcia S, Verdaguer N Proc Natl Acad Sci U S A. 2017 Jul 3;114(27):E5343-E5351. doi:, 10.1073/pnas.1702542114. Epub 2017 Jun 20. PMID:28634303[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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