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PDBsum entry 1k5w

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protein metals links
Endocytosis/exocytosis PDB id
1k5w
Jmol
Contents
Protein chain
148 a.a. *
Metals
_CA ×2
* Residue conservation analysis
PDB id:
1k5w
Name: Endocytosis/exocytosis
Title: Three-dimensional structure of the synaptotagmin 1 c2b- domain: synaptotagmin 1 as a phospholipid binding machine
Structure: Synaptotagmin i. Chain: a. Fragment: residues 270-421, c2b-domain. Synonym: syti, p65. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
NMR struc: 20 models
Authors: I.Fernandez,D.Arac,J.Ubach,S.H.Gerber,O.Shin,Y.Gao, R.G.W.Anderson,T.C.Sudhof,J.Rizo
Key ref:
I.Fernandez et al. (2001). Three-dimensional structure of the synaptotagmin 1 C2B-domain: synaptotagmin 1 as a phospholipid binding machine. Neuron, 32, 1057-1069. PubMed id: 11754837 DOI: 10.1016/S0896-6273(01)00548-7
Date:
12-Oct-01     Release date:   23-Jan-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P21707  (SYT1_RAT) -  Synaptotagmin-1
Seq:
Struc:
421 a.a.
148 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   1 term 
  Biochemical function     transporter activity     1 term  

 

 
DOI no: 10.1016/S0896-6273(01)00548-7 Neuron 32:1057-1069 (2001)
PubMed id: 11754837  
 
 
Three-dimensional structure of the synaptotagmin 1 C2B-domain: synaptotagmin 1 as a phospholipid binding machine.
I.Fernandez, D.Araç, J.Ubach, S.H.Gerber, O.Shin, Y.Gao, R.G.Anderson, T.C.Südhof, J.Rizo.
 
  ABSTRACT  
 
Synaptotagmin 1 probably functions as a Ca2+ sensor in neurotransmitter release via its two C2-domains, but no common Ca2+-dependent activity that could underlie a cooperative action between them has been described. The NMR structure of the C2B-domain now reveals a beta sandwich that exhibits striking similarities and differences with the C2A-domain. Whereas the bottom face of the C2B-domain has two additional alpha helices that may be involved in specialized Ca2+-independent functions, the top face binds two Ca2+ ions and is remarkably similar to the C2A-domain. Consistent with these results, but in contrast to previous studies, we find that the C2B-domain binds phospholipids in a Ca2+-dependent manner similarly to the C2A-domain. These results suggest a novel view of synaptotagmin function whereby the two C2-domains cooperate in a common activity, Ca2+-dependent phospholipid binding, to trigger neurotransmitter release.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Three-Dimensional Structure of the Synaptotagmin 1 C2B-Domain. (A) and (B) show superpositions of the 20 structures with the lowest NOE energies in two different orientations. (C) and (D) are ribbon diagrams of the structure of the C2B-domain in the same orientations. Strands are labeled from 1 to 8, helices are labeled HA and HB, and the Ca2+ ions (orange spheres) are labeled Ca1 and Ca2. Note that the loop connecting strands 5 and 6 forms a very short alpha-helix in some C2-domains but such helix is not observed in the structure of the synaptotagmin 1 C2B-domain. The figure was generated with the programs InsightII (MSI, San Diego, California) and Molscript (Kraulis, 1991).
Figure 7.
Figure 7. The Synaptotagmin 1 C[2]B-Domain Binds PS-Containing Vesicles in a Ca^2+-Dependent Manner(A) and (B) show FRET measurements from the C[2]A-domain (A) and C[2]B-domain (B) to phospholipid vesicles containing 10% dansyl-PE, 25% PS, and 65% PC in the presence of 0.5 mM EDTA (red traces) or 0.2 mM Ca^2+ (black traces). The protein concentration was 1 M and the lipid concentration was 0.022 mg/ml. In (B), the green trace was acquired with wild-type C[2]B-domain in 1 mM Mg^2+ and the blue trace with the D309N mutant C[2]B-domain in the presence of 0.2 mM Ca^2+. A spectrum acquired under identical conditions but without protein was subtracted for each data set. (C) and (D) show Ca^2+ dependence of phospholipid binding measured by FRET for the C[2]A-domain (C) and the C[2]B-domain (D). The relative change in FRET measured as in (A) and (B) is represented as a function of the Ca^2+ concentration for the C[2]A-domain (C) and the C[2]B-domain (D). The data represent an average of three measurements which yielded an apparent Ca^2+ affinity and Hill coefficient of 54 M Ca^2+ and 1.3, respectively, for the C[2]A-domain, and 48 M Ca^2+ and 1.6, respectively, for the C[2]B-domain. (E) shows Ca^2+-dependent phospholipid binding to the C[2]A-domain and the C[2]B-domain monitored by centrifugation. Samples containing purified GST-C[2]A-domain or GST-C[2]B-domain were incubated with liposomes (PS/PC 25:75) and various Ca^2+ concentrations as indicated. The samples were centrifuged and, after washing the precipitated liposomes, bound protein was analyzed by SDS-PAGE and Coomassie Blue staining. (F) and (G) show Ca^2+-dependent phospholipid binding to immobilized GST-C[2]A-domain (F) and GST-C[2]B-domain (G). GST fusion proteins reattached to glutathione-agarose after purification in solution were incubated with ^3H-labeled liposomes (PS/PC 30:70) at various Ca^2+ concentrations and after washing the resin, the bound lipids were measured by scintillation counting. Each graph shows a representative experiment performed in triplicate. The average apparent Ca^2+ affinity and Hill coefficient obtained from four independent experiments was 13 M Ca^2+ and 3.6, respectively, for the C[2]A-domain, and 15 M Ca^2+ and 1.7, respectively, for the C[2]B-domain. Some error bars are not visible because of their small size.
 
  The above figures are reprinted by permission from Cell Press: Neuron (2001, 32, 1057-1069) copyright 2001.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22940675 Y.Park, J.M.Hernandez, G.van den Bogaart, S.Ahmed, M.Holt, D.Riedel, and R.Jahn (2012).
Controlling synaptotagmin activity by electrostatic screening.
  Nat Struct Mol Biol, 19, 991-997.  
21642967 E.Hui, J.D.Gaffaney, Z.Wang, C.P.Johnson, C.S.Evans, and E.R.Chapman (2011).
Mechanism and function of synaptotagmin-mediated membrane apposition.
  Nat Struct Mol Biol, 18, 813-821.  
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.  
21521611 Z.P.Pang, T.Bacaj, X.Yang, P.Zhou, W.Xu, and T.C.Südhof (2011).
Doc2 supports spontaneous synaptic transmission by a Ca(2+)-independent mechanism.
  Neuron, 70, 244-251.  
20921140 C.P.Johnson, and E.R.Chapman (2010).
Otoferlin is a calcium sensor that directly regulates SNARE-mediated membrane fusion.
  J Cell Biol, 191, 187-197.  
20437249 G.J.Breedveld, G.Fabbrini, B.A.Oostra, A.Berardelli, and V.Bonifati (2010).
Tourette disorder spectrum maps to chromosome 14q31.1 in an Italian kindred.
  Neurogenetics, 11, 417-423.  
20200553 J.Rizo (2010).
Synaptotagmin-SNARE coupling enlightened.
  Nat Struct Mol Biol, 17, 260-262.  
  20824061 M.Xue, T.K.Craig, O.H.Shin, L.Li, C.A.Brautigam, D.R.Tomchick, T.C.Südhof, C.Rosenmund, and J.Rizo (2010).
Structural and mutational analysis of functional differentiation between synaptotagmins-1 and -7.
  PLoS One, 5, 0.
PDB code: 3n5a
20679236 M.Yoshihara, Z.Guan, and J.T.Littleton (2010).
Differential regulation of synchronous versus asynchronous neurotransmitter release by the C2 domains of synaptotagmin 1.
  Proc Natl Acad Sci U S A, 107, 14869-14874.  
20154707 O.H.Shin, J.Lu, J.S.Rhee, D.R.Tomchick, Z.P.Pang, S.M.Wojcik, M.Camacho-Perez, N.Brose, M.Machius, J.Rizo, C.Rosenmund, and T.C.Südhof (2010).
Munc13 C2B domain is an activity-dependent Ca2+ regulator of synaptic exocytosis.
  Nat Struct Mol Biol, 17, 280-288.
PDB codes: 3kwt 3kwu
20126653 T.Guo, L.C.Gong, and S.F.Sui (2010).
An electrostatically preferred lateral orientation of SNARE complex suggests novel mechanisms for driving membrane fusion.
  PLoS One, 5, e8900.  
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.  
20573977 Z.Zhang, E.Hui, E.R.Chapman, and M.B.Jackson (2010).
Regulation of exocytosis and fusion pores by synaptotagmin-effector interactions.
  Mol Biol Cell, 21, 2821-2831.  
19632983 A.Radhakrishnan, A.Stein, R.Jahn, and D.Fasshauer (2009).
The Ca2+ affinity of synaptotagmin 1 is markedly increased by a specific interaction of its C2B domain with phosphatidylinositol 4,5-bisphosphate.
  J Biol Chem, 284, 25749-25760.  
19501597 D.Z.Herrick, W.Kuo, H.Huang, C.D.Schwieters, J.F.Ellena, and D.S.Cafiso (2009).
Solution and membrane-bound conformations of the tandem C2A and C2B domains of synaptotagmin 1: Evidence for bilayer bridging.
  J Mol Biol, 390, 913-923.  
19703397 E.Hui, C.P.Johnson, J.Yao, F.M.Dunning, and E.R.Chapman (2009).
Synaptotagmin-mediated bending of the target membrane is a critical step in Ca(2+)-regulated fusion.
  Cell, 138, 709-721.  
19033398 N.Fukuda, M.Emoto, Y.Nakamori, A.Taguchi, S.Miyamoto, S.Uraki, Y.Oka, and Y.Tanizawa (2009).
DOC2B: a novel syntaxin-4 binding protein mediating insulin-regulated GLUT4 vesicle fusion in adipocytes.
  Diabetes, 58, 377-384.  
19805322 O.H.Shin, J.Xu, J.Rizo, and T.C.Südhof (2009).
Differential but convergent functions of Ca2+ binding to synaptotagmin-1 C2 domains mediate neurotransmitter release.
  Proc Natl Acad Sci U S A, 106, 16469-16474.  
19494235 P.N.Bernatchez, A.Sharma, P.Kodaman, and W.C.Sessa (2009).
Myoferlin is critical for endocytosis in endothelial cells.
  Am J Physiol Cell Physiol, 297, C484-C492.  
19302798 W.Kuo, D.Z.Herrick, J.F.Ellena, and D.S.Cafiso (2009).
The calcium-dependent and calcium-independent membrane binding of synaptotagmin 1: two modes of C2B binding.
  J Mol Biol, 387, 284-294.  
18308933 A.Maximov, Y.Lao, H.Li, X.Chen, J.Rizo, J.B.Sørensen, and T.C.Südhof (2008).
Genetic analysis of synaptotagmin-7 function in synaptic vesicle exocytosis.
  Proc Natl Acad Sci U S A, 105, 3986-3991.  
18650324 B.E.Paddock, A.R.Striegel, E.Hui, E.R.Chapman, and N.E.Reist (2008).
Ca2+-dependent, phospholipid-binding residues of synaptotagmin are critical for excitation-secretion coupling in vivo.
  J Neurosci, 28, 7458-7466.  
18342614 E.Connell, P.Scott, and B.Davletov (2008).
Real-time assay for monitoring membrane association of lipid-binding domains.
  Anal Biochem, 377, 83-88.  
18280495 E.Johnson, L.Bruschweiler-Li, S.A.Showalter, G.W.Vuister, F.Zhang, and R.Brüschweiler (2008).
Structure and dynamics of Ca2+-binding domain 1 of the Na+/Ca2+ exchanger in the presence and in the absence of Ca2+.
  J Mol Biol, 377, 945-955.  
18275379 E.R.Chapman (2008).
How does synaptotagmin trigger neurotransmitter release?
  Annu Rev Biochem, 77, 615-641.  
18956883 H.Huang, and D.S.Cafiso (2008).
Conformation and membrane position of the region linking the two C2 domains in synaptotagmin 1 by site-directed spin labeling.
  Biochemistry, 47, 12380-12388.  
18596818 J.Rizo, and C.Rosenmund (2008).
Synaptic vesicle fusion.
  Nat Struct Mol Biol, 15, 665-674.  
18618940 J.Rizo, and C.Rosenmund (2008).
Synaptic vesicle fusion.
  Nat Struct Mol Biol, 15, 665-674.  
18953334 M.Xue, C.Ma, T.K.Craig, C.Rosenmund, and J.Rizo (2008).
The Janus-faced nature of the C(2)B domain is fundamental for synaptotagmin-1 function.
  Nat Struct Mol Biol, 15, 1160-1168.  
18945677 N.Coudevylle, P.Montaville, A.Leonov, M.Zweckstetter, and S.Becker (2008).
Structural Determinants for Ca2+ and Phosphatidylinositol 4,5-Bisphosphate Binding by the C2A Domain of Rabphilin-3A.
  J Biol Chem, 283, 35918-35928.
PDB code: 2k3h
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.  
18849467 T.M.Mittelmeier, P.Berthold, A.Danon, M.R.Lamb, A.Levitan, M.E.Rice, and C.L.Dieckmann (2008).
C2 domain protein MIN1 promotes eyespot organization in Chlamydomonas reinhardtii.
  Eukaryot Cell, 7, 2100-2112.  
17891149 A.Stein, A.Radhakrishnan, D.Riedel, D.Fasshauer, and R.Jahn (2007).
Synaptotagmin activates membrane fusion through a Ca2+-dependent trans interaction with phospholipids.
  Nat Struct Mol Biol, 14, 904-911.  
17767192 C.M.Carr, and M.Munson (2007).
Tag team action at the synapse.
  EMBO Rep, 8, 834-838.  
17613520 C.M.Roggero, G.A.De Blas, H.Dai, C.N.Tomes, J.Rizo, and L.S.Mayorga (2007).
Complexin/synaptotagmin interplay controls acrosomal exocytosis.
  J Biol Chem, 282, 26335-26343.  
17321753 E.A.Mathews, G.P.Mullen, J.A.Crowell, J.S.Duerr, J.R.McManus, A.Duke, J.Gaskin, and J.B.Rand (2007).
Differential expression and function of synaptotagmin 1 isoforms in Caenorhabditis elegans.
  Mol Cell Neurosci, 34, 642-652.  
17320903 H.Dai, N.Shen, D.Araç, and J.Rizo (2007).
A quaternary SNARE-synaptotagmin-Ca2+-phospholipid complex in neurotransmitter release.
  J Mol Biol, 367, 848-863.  
17114221 J.A.Kertz, P.F.Almeida, A.A.Frazier, A.K.Berg, and A.Hinderliter (2007).
The cooperative response of synaptotagmin I C2A. A hypothesis for a Ca2+-driven molecular hammer.
  Biophys J, 92, 1409-1418.  
17510957 J.L.Jiménez, and B.Davletov (2007).
Beta-strand recombination in tricalbin evolution and the origin of synaptotagmin-like C2 domains.
  Proteins, 68, 770-778.  
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.  
17630786 R.Guan, H.Dai, D.R.Tomchick, I.Dulubova, M.Machius, T.C.Südhof, and J.Rizo (2007).
Crystal structure of the RIM1alpha C2B domain at 1.7 A resolution.
  Biochemistry, 46, 8988-8998.
PDB code: 2q3x
17478680 S.Martens, M.M.Kozlov, and H.T.McMahon (2007).
How synaptotagmin promotes membrane fusion.
  Science, 316, 1205-1208.  
17360437 S.W.Min, W.P.Chang, and T.C.Südhof (2007).
E-Syts, a family of membranous Ca2+-sensor proteins with multiple C2 domains.
  Proc Natl Acad Sci U S A, 104, 3823-3828.  
17156129 T.Tsuboi, E.Kanno, and M.Fukuda (2007).
The polybasic sequence in the C2B domain of rabphilin is required for the vesicle docking step in PC12 cells.
  J Neurochem, 100, 770-779.  
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.  
16267273 C.Rickman, J.L.Jiménez, M.E.Graham, D.A.Archer, M.Soloviev, R.D.Burgoyne, and B.Davletov (2006).
Conserved prefusion protein assembly in regulated exocytosis.
  Mol Biol Cell, 17, 283-294.  
16491093 D.Araç, X.Chen, H.A.Khant, J.Ubach, S.J.Ludtke, M.Kikkawa, A.E.Johnson, W.Chiu, T.C.Südhof, and J.Rizo (2006).
Close membrane-membrane proximity induced by Ca(2+)-dependent multivalent binding of synaptotagmin-1 to phospholipids.
  Nat Struct Mol Biol, 13, 209-217.  
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.  
16763567 F.Deák, O.H.Shin, J.Tang, P.Hanson, J.Ubach, R.Jahn, J.Rizo, E.T.Kavalali, and T.C.Südhof (2006).
Rabphilin regulates SNARE-dependent re-priming of synaptic vesicles for fusion.
  EMBO J, 25, 2856-2866.  
16698267 J.Rizo, X.Chen, and D.Araç (2006).
Unraveling the mechanisms of synaptotagmin and SNARE function in neurotransmitter release.
  Trends Cell Biol, 16, 339-350.  
16990140 J.Tang, A.Maximov, O.H.Shin, H.Dai, J.Rizo, and T.C.Südhof (2006).
A complexin/synaptotagmin 1 switch controls fast synaptic vesicle exocytosis.
  Cell, 126, 1175-1187.  
16715046 J.Zimmerberg, S.A.Akimov, and V.Frolov (2006).
Synaptotagmin: fusogenic role for calcium sensor?
  Nat Struct Mol Biol, 13, 301-303.  
16595652 L.Li, O.H.Shin, J.S.Rhee, D.Araç, J.C.Rah, J.Rizo, T.Südhof, and C.Rosenmund (2006).
Phosphatidylinositol phosphates as co-activators of Ca2+ binding to C2 domains of synaptotagmin 1.
  J Biol Chem, 281, 15845-15852.  
16689631 M.B.Jackson, and E.R.Chapman (2006).
Fusion pores and fusion machines in Ca2+-triggered exocytosis.
  Annu Rev Biophys Biomol Struct, 35, 135-160.  
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.  
16642042 Z.P.Pang, J.Sun, J.Rizo, A.Maximov, and T.C.Südhof (2006).
Genetic analysis of synaptotagmin 2 in spontaneous and Ca2+-triggered neurotransmitter release.
  EMBO J, 25, 2039-2050.  
16352718 J.S.Rhee, L.Y.Li, O.H.Shin, J.C.Rah, J.Rizo, T.C.Südhof, and C.Rosenmund (2005).
Augmenting neurotransmitter release by enhancing the apparent Ca2+ affinity of synaptotagmin 1.
  Proc Natl Acad Sci U S A, 102, 18664-18669.  
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.  
15528213 O.H.Shin, W.Han, Y.Wang, and T.C.Südhof (2005).
Evolutionarily conserved multiple C2 domain proteins with two transmembrane regions (MCTPs) and unusual Ca2+ binding properties.
  J Biol Chem, 280, 1641-1651.  
15561725 W.Han, J.S.Rhee, A.Maximov, W.Lin, R.E.Hammer, C.Rosenmund, and T.C.Südhof (2005).
C-terminal ECFP fusion impairs synaptotagmin 1 function: crowding out synaptotagmin 1.
  J Biol Chem, 280, 5089-5100.  
15056279 A.Nakhost, G.Houeland, V.E.Blandford, V.F.Castellucci, and W.S.Sossin (2004).
Identification and characterization of a novel C2B splice variant of synaptotagmin I.
  J Neurochem, 89, 354-363.  
14709554 C.Rickman, D.A.Archer, F.A.Meunier, M.Craxton, M.Fukuda, R.D.Burgoyne, and B.Davletov (2004).
Synaptotagmin interaction with the syntaxin/SNAP-25 dimer is mediated by an evolutionarily conserved motif and is sensitive to inositol hexakisphosphate.
  J Biol Chem, 279, 12574-12579.  
15311271 H.Dai, O.H.Shin, M.Machius, D.R.Tomchick, T.C.Südhof, and J.Rizo (2004).
Structural basis for the evolutionary inactivation of Ca2+ binding to synaptotagmin 4.
  Nat Struct Mol Biol, 11, 844-849.
PDB codes: 1w15 1w16
15491995 I.Grass, S.Thiel, S.Höning, and V.Haucke (2004).
Recognition of a basic AP-2 binding motif within the C2B domain of synaptotagmin is dependent on multimerization.
  J Biol Chem, 279, 54872-54880.  
14718921 J.Bai, W.C.Tucker, and E.R.Chapman (2004).
PIP2 increases the speed of response of synaptotagmin and steers its membrane-penetration activity toward the plasma membrane.
  Nat Struct Mol Biol, 11, 36-44.  
14718922 J.Garcia, S.H.Gerber, S.Sugita, T.C.Südhof, and J.Rizo (2004).
A conformational switch in the Piccolo C2A domain regulated by alternative splicing.
  Nat Struct Mol Biol, 11, 45-53.
PDB code: 1rh8
15146067 M.R.Wenk, and P.De Camilli (2004).
Protein-lipid interactions and phosphoinositide metabolism in membrane traffic: insights from vesicle recycling in nerve terminals.
  Proc Natl Acad Sci U S A, 101, 8262-8269.  
14983047 O.H.Shin, A.Maximov, B.K.Lim, J.Rizo, and T.C.Südhof (2004).
Unexpected Ca2+-binding properties of synaptotagmin 9.
  Proc Natl Acad Sci U S A, 101, 2554-2559.  
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.  
14704270 S.Y.Lee, M.R.Wenk, Y.Kim, A.C.Nairn, and P.De Camilli (2004).
Regulation of synaptojanin 1 by cyclin-dependent kinase 5 at synapses.
  Proc Natl Acad Sci U S A, 101, 546-551.  
15217342 T.C.Sudhof (2004).
The synaptic vesicle cycle.
  Annu Rev Neurosci, 27, 509-547.  
15454435 V.Shahrezaei, and K.R.Delaney (2004).
Consequences of molecular-level Ca2+ channel and synaptic vesicle colocalization for the Ca2+ microdomain and neurotransmitter exocytosis: a monte carlo study.
  Biophys J, 87, 2352-2364.  
15044754 W.C.Tucker, T.Weber, and E.R.Chapman (2004).
Reconstitution of Ca2+-regulated membrane fusion by synaptotagmin and SNAREs.
  Science, 304, 435-438.  
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
12496268 C.Rickman, and B.Davletov (2003).
Mechanism of calcium-independent synaptotagmin binding to target SNAREs.
  J Biol Chem, 278, 5501-5504.  
12627942 D.Araç, T.Murphy, and J.Rizo (2003).
Facile detection of protein-protein interactions by one-dimensional NMR spectroscopy.
  Biochemistry, 42, 2774-2780.  
  12939392 J.B.Sørensen, R.Fernández-Chacón, T.C.Südhof, and E.Neher (2003).
Examining synaptotagmin 1 function in dense core vesicle exocytosis under direct control of Ca2+.
  J Gen Physiol, 122, 265-276.  
12495852 L.Pallanck (2003).
A tale of two C2 domains.
  Trends Neurosci, 26, 2-4.  
12850216 M.Yoshihara, B.Adolfsen, and J.T.Littleton (2003).
Is synaptotagmin the calcium sensor?
  Curr Opin Neurobiol, 13, 315-323.  
12795692 N.Jarousse, J.D.Wilson, D.Arac, J.Rizo, and R.B.Kelly (2003).
Endocytosis of synaptotagmin 1 is mediated by a novel, tryptophan-containing motif.
  Traffic, 4, 468-478.  
12526776 O.H.Shin, J.S.Rhee, J.Tang, S.Sugita, C.Rosenmund, and T.C.Südhof (2003).
Sr2+ binding to the Ca2+ binding site of the synaptotagmin 1 C2B domain triggers fast exocytosis without stimulating SNARE interactions.
  Neuron, 37, 99.  
12963743 P.Wang, C.T.Wang, J.Bai, M.B.Jackson, and E.R.Chapman (2003).
Mutations in the effector binding loops in the C2A and C2B domains of synaptotagmin I disrupt exocytosis in a nonadditive manner.
  J Biol Chem, 278, 47030-47037.  
12746438 P.Zhong, Z.Gu, X.Wang, H.Jiang, J.Feng, and Z.Yan (2003).
Impaired modulation of GABAergic transmission by muscarinic receptors in a mouse transgenic model of Alzheimer's disease.
  J Biol Chem, 278, 26888-26896.  
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.  
11959863 D.B.Davis, K.R.Doherty, A.J.Delmonte, and E.M.McNally (2002).
Calcium-sensitive phospholipid binding properties of normal and mutant ferlin C2 domains.
  J Biol Chem, 277, 22883-22888.  
12094216 E.R.Chapman (2002).
Synaptotagmin: a Ca(2+) sensor that triggers exocytosis?
  Nat Rev Mol Cell Biol, 3, 498-508.  
12135982 I.Prudovsky, C.Bagala, F.Tarantini, A.Mandinova, R.Soldi, S.Bellum, and T.Maciag (2002).
The intracellular translocation of the components of the fibroblast growth factor 1 release complex precedes their assembly prior to export.
  J Cell Biol, 158, 201-208.  
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.  
12467593 M.Yoshihara, and J.T.Littleton (2002).
Synaptotagmin I functions as a calcium sensor to synchronize neurotransmitter release.
  Neuron, 36, 897-908.  
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.  
11739399 T.C.Südhof (2002).
Synaptotagmins: why so many?
  J Biol Chem, 277, 7629-7632.  
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.