PDBsum entry 1dqv

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protein ligands metals links
Endocytosis/exocytosis PDB id
Protein chain
275 a.a. *
_MG ×4
* Residue conservation analysis
PDB id:
Name: Endocytosis/exocytosis
Title: Crystal structure of synaptotagmin iii c2a/c2b
Structure: Synaptotagmin iii. Chain: a. Fragment: c2a/c2b. Engineered: yes. Other_details: soluble portion
Source: Rattus rattus. Black rat. Organism_taxid: 10117. Organ: brain. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PQS)
3.20Å     R-factor:   0.293     R-free:   0.348
Authors: R.B.Sutton,J.A.Ernst,A.T.Brunger
Key ref: R.B.Sutton et al. (1999). Crystal structure of the cytosolic C2A-C2B domains of synaptotagmin III. Implications for Ca(+2)-independent snare complex interaction. J Cell Biol, 147, 589-598. PubMed id: 10545502
05-Jan-00     Release date:   19-Jan-00    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P40748  (SYT3_RAT) -  Synaptotagmin-3
588 a.a.
275 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   2 terms 
  Biological process     transport   2 terms 
  Biochemical function     transporter activity     1 term  


J Cell Biol 147:589-598 (1999)
PubMed id: 10545502  
Crystal structure of the cytosolic C2A-C2B domains of synaptotagmin III. Implications for Ca(+2)-independent snare complex interaction.
R.B.Sutton, J.A.Ernst, A.T.Brunger.
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.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21642968 G.van den Bogaart, S.Thutupalli, J.H.Risselada, K.Meyenberg, M.Holt, D.Riedel, U.Diederichsen, S.Herminghaus, H.Grubmüller, and R.Jahn (2011).
Synaptotagmin-1 may be a distance regulator acting upstream of SNARE nucleation.
  Nat Struct Mol Biol, 18, 805-812.  
20200553 J.Rizo (2010).
Synaptotagmin-SNARE coupling enlightened.
  Nat Struct Mol Biol, 17, 260-262.  
20078875 M.Craxton (2010).
A manual collection of Syt, Esyt, Rph3a, Rph3al, Doc2, and Dblc2 genes from 46 metazoan genomes - an open access resource for neuroscience and evolutionary biology.
  BMC Genomics, 11, 37.  
20173762 M.Vrljic, P.Strop, J.A.Ernst, R.B.Sutton, S.Chu, and A.T.Brunger (2010).
Molecular mechanism of the synaptotagmin-SNARE interaction in Ca2+-triggered vesicle fusion.
  Nat Struct Mol Biol, 17, 325-331.
PDB code: 3hn8
20179338 T.C.Terwilliger (2010).
Rapid model building of alpha-helices in electron-density maps.
  Acta Crystallogr D Biol Crystallogr, 66, 268-275.  
20179339 T.C.Terwilliger (2010).
Rapid model building of beta-sheets in electron-density maps.
  Acta Crystallogr D Biol Crystallogr, 66, 276-284.  
20179340 T.C.Terwilliger (2010).
Rapid chain tracing of polypeptide backbones in electron-density maps.
  Acta Crystallogr D Biol Crystallogr, 66, 285-294.  
20173763 U.B.Choi, P.Strop, M.Vrljic, S.Chu, A.T.Brunger, and K.R.Weninger (2010).
Single-molecule FRET-derived model of the synaptotagmin 1-SNARE fusion complex.
  Nat Struct Mol Biol, 17, 318-324.  
19489736 A.T.Brunger, K.Weninger, M.Bowen, and S.Chu (2009).
Single-molecule studies of the neuronal SNARE fusion machinery.
  Annu Rev Biochem, 78, 903-928.  
19358157 K.E.Mace, L.M.Biela, A.G.Sares, and N.E.Reist (2009).
Synaptotagmin I stabilizes synaptic vesicles via its C(2)A polylysine motif.
  Genesis, 47, 337-345.  
19186144 K.L.Fuson, L.Ma, R.B.Sutton, and A.F.Oberhauser (2009).
The c2 domains of human synaptotagmin 1 have distinct mechanical properties.
  Biophys J, 96, 1083-1090.  
20023730 M.H.Abdulreda, A.Bhalla, F.Rico, P.O.Berggren, E.R.Chapman, and V.T.Moy (2009).
Pulling force generated by interacting SNAREs facilitates membrane hemifusion.
  Integr Biol (Camb), 1, 301-310.  
  20228892 M.H.Abdulreda, and V.T.Moy (2009).
Investigation of SNARE-Mediated Membrane Fusion Mechanism Using Atomic Force Microscopy.
  Jpn J Appl Phys (2008), 48, 8JA03.  
18508778 A.Bhalla, M.C.Chicka, and E.R.Chapman (2008).
Analysis of the synaptotagmin family during reconstituted membrane fusion. Uncovering a class of inhibitory isoforms.
  J Biol Chem, 283, 21799-21807.  
18275379 E.R.Chapman (2008).
How does synaptotagmin trigger neurotransmitter release?
  Annu Rev Biochem, 77, 615-641.  
18596155 R.Friedrich, A.J.Groffen, E.Connell, J.R.van Weering, O.Gutman, Y.I.Henis, B.Davletov, and U.Ashery (2008).
DOC2B acts as a calcium switch and enhances vesicle fusion.
  J Neurosci, 28, 6794-6806.  
18496517 S.Martens, and H.T.McMahon (2008).
Mechanisms of membrane fusion: disparate players and common principles.
  Nat Rev Mol Cell Biol, 9, 543-556.  
17767192 C.M.Carr, and M.Munson (2007).
Tag team action at the synapse.
  EMBO Rep, 8, 834-838.  
17914059 K.L.Lynch, R.R.Gerona, E.C.Larsen, R.F.Marcia, J.C.Mitchell, and T.F.Martin (2007).
Synaptotagmin C2A loop 2 mediates Ca2+-dependent SNARE interactions essential for Ca2+-triggered vesicle exocytosis.
  Mol Biol Cell, 18, 4957-4968.  
17547707 L.Glover, and R.H.Brown (2007).
Dysferlin in membrane trafficking and patch repair.
  Traffic, 8, 785-794.  
17585869 M.A.Zhukovsky, I.Markovic, and A.L.Bailey (2007).
Influence of calcium on lipid mixing mediated by influenza hemagglutinin.
  Arch Biochem Biophys, 465, 101-108.  
18158333 M.Dong, W.H.Tepp, H.Liu, E.A.Johnson, and E.R.Chapman (2007).
Mechanism of botulinum neurotoxin B and G entry into hippocampal neurons.
  J Cell Biol, 179, 1511-1522.  
16515538 A.J.Groffen, R.Friedrich, E.C.Brian, U.Ashery, and M.Verhage (2006).
DOC2A and DOC2B are sensors for neuronal activity with unique calcium-dependent and kinetic properties.
  J Neurochem, 97, 818-833.  
16528727 C.A.Loewen, S.M.Royer, and N.E.Reist (2006).
Drosophila synaptotagmin I null mutants show severe alterations in vesicle populations but calcium-binding motif mutants do not.
  J Comp Neurol, 496, 1.  
16782782 E.Hui, J.Bai, and E.R.Chapman (2006).
Ca2+-triggered simultaneous membrane penetration of the tandem C2-domains of synaptotagmin I.
  Biophys J, 91, 1767-1777.  
17124515 I.Voskoboinik, M.J.Smyth, and J.A.Trapani (2006).
Perforin-mediated target-cell death and immune homeostasis.
  Nat Rev Immunol, 6, 940-952.  
16790935 M.Biadene, P.Montaville, G.M.Sheldrick, and S.Becker (2006).
Structure of the C2A domain of rabphilin-3A.
  Acta Crystallogr D Biol Crystallogr, 62, 793-799.
PDB code: 2chd
16572466 M.Leguia, S.Conner, L.Berg, and G.M.Wessel (2006).
Synaptotagmin I is involved in the regulation of cortical granule exocytosis in the sea urchin.
  Mol Reprod Dev, 73, 895-905.  
  16946482 M.Montes, K.L.Fuson, R.B.Sutton, and J.J.Robert (2006).
Purification, crystallization and X-ray diffraction analysis of human synaptotagmin 1 C2A-C2B.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 926-929.  
17167418 Q.Chai, J.W.Arndt, M.Dong, W.H.Tepp, E.A.Johnson, E.R.Chapman, and R.C.Stevens (2006).
Structural basis of cell surface receptor recognition by botulinum neurotoxin B.
  Nature, 444, 1096-1100.
PDB code: 2np0
15793006 E.Hui, J.Bai, P.Wang, M.Sugimori, R.R.Llinas, and E.R.Chapman (2005).
Three distinct kinetic groupings of the synaptotagmin family: candidate sensors for rapid and delayed exocytosis.
  Proc Natl Acad Sci U S A, 102, 5210-5214.  
15821166 M.E.Bowen, K.Weninger, J.Ernst, S.Chu, and A.T.Brunger (2005).
Single-molecule studies of synaptotagmin and complexin binding to the SNARE complex.
  Biophys J, 89, 690-702.  
16168654 N.W.Andrews, and S.Chakrabarti (2005).
There's more to life than neurotransmission: the regulation of exocytosis by synaptotagmin VII.
  Trends Cell Biol, 15, 626-631.  
15238157 M.Craxton (2004).
Synaptotagmin gene content of the sequenced genomes.
  BMC Genomics, 5, 43.  
15041683 R.A.García, and H.A.Godwin (2004).
High metal concentrations are required for self-association of synaptotagmin II.
  Biophys J, 86, 2455-2466.  
15591349 R.R.Llinás, M.Sugimori, K.A.Moran, J.E.Moreira, and M.Fukuda (2004).
Vesicular reuptake inhibition by a synaptotagmin I C2B domain antibody at the squid giant synapse.
  Proc Natl Acad Sci U S A, 101, 17855-17860.  
15340165 Y.Cheng, S.M.Sequeira, L.Malinina, V.Tereshko, T.H.Söllner, and D.J.Patel (2004).
Crystallographic identification of Ca2+ and Sr2+ coordination sites in synaptotagmin I C2B domain.
  Protein Sci, 13, 2665-2672.
PDB codes: 1tjm 1tjx 1uov 1uow
12948775 L.K.Tamm, J.Crane, and V.Kiessling (2003).
Membrane fusion: a structural perspective on the interplay of lipids and proteins.
  Curr Opin Struct Biol, 13, 453-466.  
12900172 T.W.Koh, and H.J.Bellen (2003).
Synaptotagmin I, a Ca2+ sensor for neurotransmitter release.
  Trends Neurosci, 26, 413-422.  
12578982 Y.Wu, Y.He, J.Bai, S.R.Ji, W.C.Tucker, E.R.Chapman, and S.F.Sui (2003).
Visualization of synaptotagmin I oligomers assembled onto lipid monolayers.
  Proc Natl Acad Sci U S A, 100, 2082-2087.  
12009889 A.A.Frazier, M.A.Wisner, N.J.Malmberg, K.G.Victor, G.E.Fanucci, E.A.Nalefski, J.J.Falke, and D.S.Cafiso (2002).
Membrane orientation and position of the C2 domain from cPLA2 by site-directed spin labeling.
  Biochemistry, 41, 6282-6292.  
12094216 E.R.Chapman (2002).
Synaptotagmin: a Ca(2+) sensor that triggers exocytosis?
  Nat Rev Mol Cell Biol, 3, 498-508.  
11805296 J.Bai, P.Wang, and E.R.Chapman (2002).
C2A activates a cryptic Ca(2+)-triggered membrane penetration activity within the C2B domain of synaptotagmin I.
  Proc Natl Acad Sci U S A, 99, 1665-1670.  
12110842 J.M.Mackler, J.A.Drummond, C.A.Loewen, I.M.Robinson, and N.E.Reist (2002).
The C(2)B Ca(2+)-binding motif of synaptotagmin is required for synaptic transmission in vivo.
  Nature, 418, 340-344.  
11823420 S.Sugita, O.H.Shin, W.Han, Y.Lao, and T.C.Südhof (2002).
Synaptotagmins form a hierarchy of exocytotic Ca(2+) sensors with distinct Ca(2+) affinities.
  EMBO J, 21, 270-280.  
11340056 A.T.Brunger (2001).
Structure of proteins involved in synaptic vesicle fusion in neurons.
  Annu Rev Biophys Biomol Struct, 30, 157-171.  
11297924 A.T.Brunger (2001).
Structural insights into the molecular mechanism of calcium-dependent vesicle-membrane fusion.
  Curr Opin Struct Biol, 11, 163-173.  
11551981 C.A.Earles, J.Bai, P.Wang, and E.R.Chapman (2001).
The tandem C2 domains of synaptotagmin contain redundant Ca2+ binding sites that cooperate to engage t-SNAREs and trigger exocytosis.
  J Cell Biol, 154, 1117-1123.  
11259490 C.M.Bouton, L.P.Frelin, C.E.Forde, H.Arnold Godwin, and J.Pevsner (2001).
Synaptotagmin I is a molecular target for lead.
  J Neurochem, 76, 1724-1735.  
11359862 D.Atlas (2001).
Functional and physical coupling of voltage-sensitive calcium channels with exocytotic proteins: ramifications for the secretion mechanism.
  J Neurochem, 77, 972-985.  
11517928 D.Reverter, S.Strobl, C.Fernandez-Catalan, H.Sorimachi, K.Suzuki, and W.Bode (2001).
Structural basis for possible calcium-induced activation mechanisms of calpains.
  Biol Chem, 382, 753-766.  
11342594 E.V.Caler, S.Chakrabarti, K.T.Fowler, S.Rao, and N.W.Andrews (2001).
The Exocytosis-regulatory protein synaptotagmin VII mediates cell invasion by Trypanosoma cruzi.
  J Exp Med, 193, 1097-1104.  
11687498 F.M.Brodsky, C.Y.Chen, C.Knuehl, M.C.Towler, and D.E.Wakeham (2001).
Biological basket weaving: formation and function of clathrin-coated vesicles.
  Annu Rev Cell Dev Biol, 17, 517-568.  
11399430 G.J.Augustine (2001).
How does calcium trigger neurotransmitter release?
  Curr Opin Neurobiol, 11, 320-326.  
11282351 H.A.Godwin (2001).
The biological chemistry of lead.
  Curr Opin Chem Biol, 5, 223-227.  
11413542 J.M.Mackler, and N.E.Reist (2001).
Mutations in the second C2 domain of synaptotagmin disrupt synaptic transmission at Drosophila neuromuscular junctions.
  J Comp Neurol, 436, 4.  
11331402 M.Fukuda, K.Ibata, and K.Mikoshiba (2001).
A unique spacer domain of synaptotagmin IV is essential for Golgi localization.
  J Neurochem, 77, 730-740.  
11423412 M.L.Wagner, and L.K.Tamm (2001).
Reconstituted syntaxin1a/SNAP25 interacts with negatively charged lipids as measured by lateral diffusion in planar supported bilayers.
  Biophys J, 81, 266-275.  
11239400 Y.Mao, J.Chen, J.A.Maynard, B.Zhang, and F.A.Quiocho (2001).
A novel all helix fold of the AP180 amino-terminal domain for phosphoinositide binding and clathrin assembly in synaptic vesicle endocytosis.
  Cell, 104, 433-440.
PDB code: 1hx8
10851178 A.T.Brunger (2000).
Structural insights into the molecular mechanism of Ca(2+)-dependent exocytosis.
  Curr Opin Neurobiol, 10, 293-302.  
10933784 B.Mehrotra, D.G.Myszka, and G.D.Prestwich (2000).
Binding kinetics and ligand specificity for the interactions of the C2B domain of synaptogmin II with inositol polyphosphates and phosphoinositides.
  Biochemistry, 39, 9679-9686.  
11042461 B.R.Lentz, V.Malinin, M.E.Haque, and K.Evans (2000).
Protein machines and lipid assemblies: current views of cell membrane fusion.
  Curr Opin Struct Biol, 10, 607-615.  
11208133 J.A.Ybe, D.E.Wakeham, F.M.Brodsky, and P.K.Hwang (2000).
Molecular structures of proteins involved in vesicle fusion.
  Traffic, 1, 474-479.  
11114503 K.M.Misura, A.P.May, and W.I.Weis (2000).
Protein-protein interactions in intracellular membrane fusion.
  Curr Opin Struct Biol, 10, 662-671.  
10811903 R.A.García, C.E.Forde, and H.A.Godwin (2000).
Calcium triggers an intramolecular association of the C2 domains in synaptotagmin.
  Proc Natl Acad Sci U S A, 97, 5883-5888.  
10974000 R.C.Desai, B.Vyas, C.A.Earles, J.T.Littleton, J.A.Kowalchyck, T.F.Martin, and E.R.Chapman (2000).
The C2B domain of synaptotagmin is a Ca(2+)-sensing module essential for exocytosis.
  J Cell Biol, 150, 1125-1136.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.