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PMID: 10811903 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Calcium triggers an intramolecular association of the C2 domains in synaptotagmin.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 97 ·No. 11 ·2000-05-23 ·Pages 5883-8

García RA, Forde CE, Godwin HA

Abstract

Synaptotagmin I is a critical component of the synaptic machinery that senses calcium influx and triggers synaptic vesicle fusion and neurotransmitter release. Fluorescence resonance energy transfer studies conducted on synaptotagmin demonstrate that calcium concentrations required for fusion induce a conformational change (EC(50) approximately 3 mM) that brings the two calcium-binding C2 domains in synaptotagmin closer together. Analytical ultracentrifugation studies reveal that synaptotagmin is monomeric under these conditions, indicating that this calcium-triggered association between the C2 domains is intramolecular, rather than intermolecular. These results suggest a mechanism for synaptotagmin function at the presynaptic plasma membrane that involves the self-association of C2 domains.

MeSH Terms
Amino Acid Sequence Calcium/pharmacology Calcium-Binding Proteins Membrane Glycoproteins/chemistry,drug effects Molecular Sequence Data Molecular Weight Nerve Tissue Proteins/chemistry,drug effects Protein Structure, Tertiary Synaptotagmin I Synaptotagmins Ultracentrifugation
Chemicals
Calcium-Binding Proteins Membrane Glycoproteins Nerve Tissue Proteins Synaptotagmin I Synaptotagmins Calcium
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
García R A
Department of Biochemistry, Molecular Biology, and Cell Biology, 2153 North Campus Drive, Northwestern University, Evanston, IL 60208-3300, USA.
Forde C E
Godwin H A
References (41)
41 references, click to expand
  1. Crystal structure of the cytosolic C2A-C2B domains of synaptotagmin III. Implications for Ca(+2)-independent snare complex interaction.
    J Cell Biol. 1999 Nov 1;147(3):589-98 PMID: 10545502
  2. The C2 domain calcium-binding motif: structural and functional diversity.
    Protein Sci. 1996 Dec;5(12):2375-90 PMID: 8976547
  3. Phospholipid binding by a synaptic vesicle protein homologous to the regulatory region of protein kinase C.
    Nature. 1990 May 17;345(6272):260-3 PMID: 2333096
  4. Microdomains of high calcium concentration in a presynaptic terminal.
    Science. 1992 May 1;256(5057):677-9 PMID: 1350109
  5. Synaptotagmin: a calcium sensor on the synaptic vesicle surface.
    Science. 1992 May 15;256(5059):1021-5 PMID: 1589771
  6. Membrane fusion.
    Science. 1992 Nov 6;258(5084):917-24 PMID: 1439803
  7. Rabphilin-3A, a putative target protein for smg p25A/rab3A p25 small GTP-binding protein related to synaptotagmin.
    Mol Cell Biol. 1993 Apr;13(4):2061-8 PMID: 8384302
  8. A single C2 domain from synaptotagmin I is sufficient for high affinity Ca2+/phospholipid binding.
    J Biol Chem. 1993 Dec 15;268(35):26386-90 PMID: 8253763
  9. Calcium-dependent interaction of the cytoplasmic region of synaptotagmin with membranes. Autonomous function of a single C2-homologous domain.
    J Biol Chem. 1994 Feb 25;269(8):5735-41 PMID: 8119912
  10. Ca(2+)-dependent conformational change in synaptotagmin I.
    J Biol Chem. 1994 Nov 18;269(46):28547-50 PMID: 7961798
  11. Two components of transmitter release at a central synapse.
    Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12942-6 PMID: 7809151
  12. Synaptotagmin-syntaxin interaction: the C2 domain as a Ca2+-dependent electrostatic switch.
    Neuron. 1997 Jan;18(1):133-42 PMID: 9010211
  13. Binding of the synaptic vesicle v-SNARE, synaptotagmin, to the plasma membrane t-SNARE, SNAP-25, can explain docked vesicles at neurotoxin-treated synapses.
    Proc Natl Acad Sci U S A. 1997 Feb 4;94(3):997-1001 PMID: 9023371
  14. A ternary metal binding site in the C2 domain of phosphoinositide-specific phospholipase C-delta1.
    Biochemistry. 1997 Mar 11;36(10):2753-62 PMID: 9062102
  15. Crystal structure of a calcium-phospholipid binding domain from cytosolic phospholipase A2.
    J Biol Chem. 1998 Jan 16;273(3):1596-604 PMID: 9430701
  16. C2-domains, structure and function of a universal Ca2+-binding domain.
    J Biol Chem. 1998 Jun 26;273(26):15879-82 PMID: 9632630
  17. Mutagenesis of the C2 domain of protein kinase C-alpha. Differential roles of Ca2+ ligands and membrane binding residues.
    J Biol Chem. 1998 Jul 10;273(28):17544-52 PMID: 9651347
  18. Solution structure and membrane interactions of the C2 domain of cytosolic phospholipase A2.
    J Mol Biol. 1998 Jul 17;280(3):485-500 PMID: 9665851
  19. Calcium-dependent membrane penetration is a hallmark of the C2 domain of cytosolic phospholipase A2 whereas the C2A domain of synaptotagmin binds membranes electrostatically.
    J Biol Chem. 1998 Jul 24;273(30):19093-6 PMID: 9668093
  20. Ca2+ binding to synaptotagmin: how many Ca2+ ions bind to the tip of a C2-domain?
    EMBO J. 1998 Jul 15;17(14):3921-30 PMID: 9670009
  21. Mechanism of phospholipid binding by the C2A-domain of synaptotagmin I.
    Biochemistry. 1998 Sep 8;37(36):12395-403 PMID: 9730811
  22. Lipid binding ridge on loops 2 and 3 of the C2A domain of synaptotagmin I as revealed by NMR spectroscopy.
    J Biol Chem. 1998 Oct 2;273(40):25659-63 PMID: 9748232
  23. Three-dimensional structure of an evolutionarily conserved N-terminal domain of syntaxin 1A.
    Cell. 1998 Sep 18;94(6):841-9 PMID: 9753330
  24. Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 A resolution.
    Nature. 1998 Sep 24;395(6700):347-53 PMID: 9759724
  25. Mechanics of membrane fusion.
    Nat Struct Biol. 1998 Oct;5(10):839-42 PMID: 9783736
  26. Solution structures of the Ca2+-free and Ca2+-bound C2A domain of synaptotagmin I: does Ca2+ induce a conformational change?
    Biochemistry. 1998 Nov 17;37(46):16106-15 PMID: 9819203
  27. Delineation of the oligomerization, AP-2 binding, and synprint binding region of the C2B domain of synaptotagmin.
    J Biol Chem. 1998 Dec 4;273(49):32966-72 PMID: 9830048
  28. Classification and evolution of EF-hand proteins.
    Biometals. 1998 Dec;11(4):277-95 PMID: 10191494
  29. Structures of EF-hand Ca(2+)-binding proteins: diversity in the organization, packing and response to Ca2+ binding.
    Biometals. 1998 Dec;11(4):297-318 PMID: 10191495
  30. Doc2: a novel brain protein having two repeated C2-like domains.
    Biochem Biophys Res Commun. 1995 Jan 17;206(2):439-48 PMID: 7826360
  31. Structure of the first C2 domain of synaptotagmin I: a novel Ca2+/phospholipid-binding fold.
    Cell. 1995 Mar 24;80(6):929-38 PMID: 7697723
  32. Neural transmission. Synaptotagmin is just a calcium sensor.
    Curr Biol. 1995 Mar 1;5(3):257-9 PMID: 7780734
  33. Ca2+ regulates the interaction between synaptotagmin and syntaxin 1.
    J Biol Chem. 1995 Oct 6;270(40):23667-71 PMID: 7559535
  34. Distinct Ca2+ and Sr2+ binding properties of synaptotagmins. Definition of candidate Ca2+ sensors for the fast and slow components of neurotransmitter release.
    J Biol Chem. 1995 Oct 20;270(42):24898-902 PMID: 7559614
  35. Localization of synaptotagmin-binding domains on syntaxin.
    J Neurosci. 1996 Mar 15;16(6):1975-81 PMID: 8604041
  36. Crystal structure of a mammalian phosphoinositide-specific phospholipase C delta.
    Nature. 1996 Apr 18;380(6575):595-602 PMID: 8602259
  37. A novel function for the second C2 domain of synaptotagmin. Ca2+-triggered dimerization.
    J Biol Chem. 1996 Mar 8;271(10):5844-9 PMID: 8621455
  38. Bipartite Ca2+-binding motif in C2 domains of synaptotagmin and protein kinase C.
    Science. 1996 Jul 12;273(5272):248-51 PMID: 8662510
  39. Calcium binding and conformational response in EF-hand proteins.
    Trends Biochem Sci. 1996 Jan;21(1):14-7 PMID: 8848832
  40. Calcium-dependent self-association of synaptotagmin I.
    J Neurochem. 1996 Oct;67(4):1661-8 PMID: 8858951
  41. Energy transfer: a spectroscopic ruler.
    Proc Natl Acad Sci U S A. 1967 Aug;58(2):719-26 PMID: 5233469
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.100127197
Published
2000-05-23
Pages
5883-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC18528
Subset
IM
Grants
NIGMS NIH HHS · R01 GM058183 · United States
NIGMS NIH HHS · T32 GM008061 · United States
NIGMS NIH HHS · 1 R01 GM58183-01A1 · United States
NIGMS NIH HHS · T32 GM08061 · United States
External Links
PubMed source DOI: 10.1073/pnas.100127197 PMC Full Text View journal details
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