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• W1418660035 abstract "The synaptotagmin (Syt) family of proteins plays an important role in vesicle docking and fusion during Ca(2+)-induced exocytosis in a wide variety of cell types. Its role as a Ca(2+) sensor derives primarily from its two C2 domains, C2A and C2B, which insert into anionic lipid membranes upon binding Ca(2+). Syt isoforms 1 and 7 differ significantly in their Ca(2+) sensitivity; the C2A domain from Syt7 binds Ca(2+) and membranes much more tightly than the C2A domain from Syt1, at least in part because of greater contributions from the hydrophobic effect. While the structure and membrane activity of Syt1 have been extensively studied, the structural origins of differences between Syt1 and Syt7 are unknown. This study used site-directed spin labeling and electron paramagnetic resonance spectroscopy to determine depth parameters for the Syt7 C2A domain, for comparison to analogous previous measurements with the Syt1 C2A domain. In a novel approach, the membrane docking geometry of both Syt1 and Syt7 C2A was modeled by mapping depth parameters onto multiple molecular dynamics-simulated structures of the Ca(2+)-bound protein. The models reveal membrane penetration of Ca(2+) binding loops 1 (CBL1) and 3 (CBL3), and membrane binding is more sensitive to mutations in CBL3. On average, Syt7 C2A inserts more deeply into the membrane than Syt1 C2A, although depths vary among the different structural models. This observation provides a partial structural explanation for the hydrophobically driven membrane docking of Syt7 C2A." @default.
• W1418660035 created "2016-06-24" @default.
• W1418660035 creator A5008303385 @default.
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• W1418660035 date "2015-09-10" @default.
• W1418660035 modified "2023-10-15" @default.
• W1418660035 title "Membrane Docking of the Synaptotagmin 7 C2A Domain: Electron Paramagnetic Resonance Measurements Show Contributions from Two Membrane Binding Loops" @default.
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• W1418660035 doi "https://doi.org/10.1021/acs.biochem.5b00421" @default.
• W1418660035 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4630001" @default.
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• W1418660035 hasPublicationYear "2015" @default.
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