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PMID: 10545502 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Crystal structure of the cytosolic C2A-C2B domains of synaptotagmin III. Implications for Ca(+2)-independent snare complex interaction.

The Journal of cell biology ·Vol. 147 ·No. 3 ·1999-11-01 ·Pages 589-98

Sutton RB, Ernst JA, Brunger AT

Abstract

Synaptotagmins are synaptic vesicle-associated, phospholipid-binding proteins most commonly associated with Ca(+2)-dependent exocytotic and Ca(+2)- independent endocytotic events. Synaptotagmin III is a 63.2-kD member of the synaptotagmin homology group; one of its characteristic properties is the ability to bind divalent cations and accessory proteins promiscuously. In the cytosolic portion of this protein, a flexible seven-amino acid linker joins two homologous C2 domains. The C2A domain binds to phospholipid membranes and other accessory proteins in a divalent cation-dependent fashion. The C2B domain promotes binding to other C2B domains, as well as accessory proteins independent of divalent cations. The 3.2 A crystal structure of synaptotagmin III, residues 295-566, which includes the C2A and C2B domains, exhibits differences in the shape of the Ca(+2)-binding pocket, the electrostatic surface potential, and the stoichiometry of bound divalent cations for the two domains. These observations may explain the disparate binding properties of the two domains. The C2A and the C2B domains do not interact; synaptotagmin, therefore, covalently links two independent C2 domains, each with potentially different binding partners. A model of synaptotagmin's involvement in Ca(+2)-dependent regulation of membrane fusion through its interaction with the SNARE complex is presented.

MeSH Terms
Amino Acid Sequence Animals Binding Sites Calcium/metabolism Calcium-Binding Proteins Crystallization Crystallography, X-Ray Magnesium/metabolism Membrane Fusion Membrane Glycoproteins/chemistry,genetics,isolation & purification,metabolism Membrane Proteins/isolation & purification,metabolism Mice Models, Molecular Molecular Sequence Data Nerve Tissue Proteins/chemistry,genetics,isolation & purification,metabolism Peptide Fragments/chemistry,genetics,isolation & purification,metabolism Protein Isoforms/chemistry,genetics,isolation & purification,metabolism Protein Structure, Secondary Rats SNARE Proteins Sequence Alignment Static Electricity Synaptotagmins Vesicular Transport Proteins
Chemicals
Calcium-Binding Proteins Membrane Glycoproteins Membrane Proteins Nerve Tissue Proteins Peptide Fragments Protein Isoforms SNARE Proteins Syt3 protein, mouse Syt3 protein, rat Vesicular Transport Proteins Synaptotagmins Magnesium Calcium
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Sutton R B
The Howard Hughes Medical Institute, Yale University, New Haven, Connecticut 06520, USA.
Ernst J A
Brunger A T
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.147.3.589
Published
1999-11-01
Pages
589-98
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2151181
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.147.3.589 PMC Full Text View journal details
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