5LOW

Structure of the Ca2+-bound Rabphilin 3A C2B domain SNAP25 complex (P21 space group)

Summary for 5LOW

• Entry DOI: 10.2210/pdb5low/pdb
• Descriptor: Rabphilin-3A, Synaptosomal-associated protein 25, GLYCEROL, ... (6 entities in total)
• Functional Keywords: membrane fusion, calcium, c2 domain, exocytosis
• Biological source: Rattus norvegicus (Norway Rat); More
• Cellular location: Cell junction, synapse : P47709; Cytoplasm, perinuclear region : P60881 P60881
• Total number of polymer chains: 14
• Total formula weight: 192858.82

Authors

Verdaguer, N.,Ferrer-Orta, C. (deposition date: 2016-08-10, release date: 2017-06-21, Last modification date: 2024-01-10)

Primary citation

Ferrer-Orta, C.,Perez-Sanchez, M.D.,Coronado-Parra, T.,Silva, C.,Lopez-Martinez, D.,Baltanas-Copado, J.,Gomez-Fernandez, J.C.,Corbalan-Garcia, S.,Verdaguer, N.
Structural characterization of the Rabphilin-3A-SNAP25 interaction.
Proc. Natl. Acad. Sci. U.S.A., 114:E5343-E5351, 2017

PubMed Abstract: Membrane 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 (PIP) complexes, revealing how Rabphilin-3A C2 domains operate in cooperation with PIP/Ca 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-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.

PubMed: 28634303
DOI: 10.1073/pnas.1702542114

Experimental method

X-RAY DIFFRACTION (2.8 Å)