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- Title
Close membrane-membrane proximity induced by Ca<sup>2+</sup>-dependent multivalent binding of synaptotagmin-1 to phospholipids.
- Authors
Araç, Demet; Xiaocheng Chen; Khant, Htet A.; Ubach, Josep; Ludtke, Steven J.; Kikkawa, Masahide; Johnson, Arthur E.; Wah Chiu; Südhof, Thomas C.; Rizo, Josep
- Abstract
Synaptotagmin acts as a Ca2+ sensor in neurotransmitter release through its two C2 domains. Ca2+-dependent phospholipid binding is key for synaptotagmin function, but it is unclear how this activity cooperates with the SNARE complex involved in release or why Ca2+ binding to the C2B domain is more crucial for release than Ca2+ binding to the C2A domain. Here we show that Ca2+ induces high-affinity simultaneous binding of synaptotagmin to two membranes, bringing them into close proximity. The synaptotagmin C2B domain is sufficient for this ability, which arises from the abundance of basic residues around its surface. We propose a model wherein synaptotagmin cooperates with the SNAREs in bringing the synaptic vesicle and plasma membranes together and accelerates membrane fusion through the highly positive electrostatic potential of its C2B domain.
- Publication
Nature Structural & Molecular Biology, 2006, Vol 13, Issue 3, p209
- ISSN
1545-9993
- Publication type
Academic Journal
- DOI
10.1038/nsmb1056