Structure of Human Synaptotagmin 1 C2AB in the Absence of Ca**2+ Reveals a Novel Domain Association
Release of neurotransmitter from synaptic vesicles requires the Ca{sup 2+}/phospholipid-binding protein synaptotagmin 1. There is considerable evidence that cooperation between the tandem C2 domains of synaptotagmin is a requirement of regulated exocytosis; however, high-resolution structural evidence for this interaction has been lacking. The 2.7 A crystal structure of the cytosolic domains of human synaptotagmin 1 in the absence of Ca{sup 2+} reveals a novel closed conformation of the protein. The shared interface between C2A and C2B is stabilized by a network of interactions between residues on the C-terminal alpha-helix of the C2B domain and residues on loops 1-3 of the Ca{sup 2+}-binding region of C2A. These interactions alter the overall shape of the Ca{sup 2+}-binding pocket of C2A, but not that of C2B. Thus, synaptotagmin 1 C2A-C2B may utilize a novel regulatory mechanism whereby one C2 domain could regulate the other until an appropriate triggering event decouples them.
- Research Organization:
- Stanford Linear Accelerator Center (SLAC)
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- AC02-76SF00515
- OSTI ID:
- 953982
- Report Number(s):
- SLAC-REPRINT-2009-410
- Journal Information:
- Biochem. 46:13041,2007, Journal Name: Biochem. 46:13041,2007 Journal Issue: 45 Vol. 46; ISSN 0006-2960; ISSN BICHAW
- Country of Publication:
- United States
- Language:
- English
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