Structural characterization of the Rabphilin-3A-SNAP25 interaction [Biophysics and Computational Biology]
![Structural characterization of the Rabphilin-3A-SNAP25 interaction [Biophysics and Computational Biology]](/image/eyJ1cmkiOiJodHRwOi8vd3d3LnBuYXMub3JnL2NvbnRlbnQvZWFybHkvMjAxNy8wNi8xOS8xNzAyNTQyMTE0L0YxLm1lZGl1bS5naWYiLCJmb3JtYXQiOiJ3ZWJwIiwicXVhbGl0eSI6MTAwLCJub0NhY2hlIjp0cnVlfQ==.webp)
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 (PIP2) complexes, revealing how Rabphilin-3A C2 domains operate in cooperation with PIP2/Ca2+ 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 Ca2+-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.
Publisher URL: http://feedproxy.google.com/~r/Pnas-RssFeedOfEarlyEditionArticles/~3/yn4vKK21nAs/1702542114.short
DOI: 10.1073/pnas.1702542114
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