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Biochemistry. 2007 Nov 13;46(45):13041-8. Epub 2007 Oct 23.

Structure of human synaptotagmin 1 C2AB in the absence of Ca2+ reveals a novel domain association.

Author information

1
Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, Texas 77555, USA.

Abstract

Release of neurotransmitter from synaptic vesicles requires the Ca2+/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 Ca2+ 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 Ca2+-binding region of C2A. These interactions alter the overall shape of the Ca2+-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.

PMID:
17956130
PMCID:
PMC5975968
DOI:
10.1021/bi701651k
[Indexed for MEDLINE]
Free PMC Article

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