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PDBsum entry 1rsy
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Calcium/phospholipid binding protein PDB id
1rsy

 

 

 

 

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Contents
Protein chain
135 a.a. *
Ligands
SO4
Waters ×80
* Residue conservation analysis
PDB id:
1rsy
Name: Calcium/phospholipid binding protein
Title: Structure of the first c2-domain of synaptotagmin i: a novel ca2+(slash)phospholipid binding fold
Structure: Synaptotagmin i. Chain: a. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.90Å     R-factor:   0.186     R-free:   0.249
Authors: R.B.Sutton,S.R.Sprang
Key ref: R.B.Sutton et al. (1995). Structure of the first C2 domain of synaptotagmin I: a novel Ca2+/phospholipid-binding fold. Cell, 80, 929-938. PubMed id: 7697723 DOI: 10.1016/0092-8674(95)90296-1
Date:
01-Feb-95     Release date:   08-May-95    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P21707  (SYT1_RAT) -  Synaptotagmin-1 from Rattus norvegicus
Seq:
Struc: 		421 a.a.
135 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 9 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.?
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

 

 
DOI no: 10.1016/0092-8674(95)90296-1 Cell 80:929-938 (1995)
PubMed id: 7697723  
 
 
Structure of the first C2 domain of synaptotagmin I: a novel Ca2+/phospholipid-binding fold.
R.B.Sutton, B.A.Davletov, A.M.Berghuis, T.C.Südhof, S.R.Sprang.
 
  ABSTRACT  
 
C2 domains are regulatory sequence motifs that occur widely in nature. Synaptotagmin I, a synaptic vesicle protein involved in the Ca2+ regulation of exocytosis, contains two C2 domains, the first of which acts as a Ca2+ sensor. We now describe the three-dimensional structure of this C2 domain at 1.9 A resolution in both the Ca(2+)-bound and Ca(2+)-free forms. The C2 polypeptide forms an eight-stranded beta sandwich constructed around a conserved four-stranded motif designated as a C2 key. Ca2+ binds in a cup-shaped depression between two polypeptide loops located at the N- and C-termini of the C2-key motif.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21294713 G.Ankem, S.Mitra, F.Sun, A.C.Moreno, B.Chutvirasakul, H.F.Azurmendi, L.Li, and D.G.Capelluto (2011).
The C2 domain of Tollip, a Toll-like receptor signalling regulator, exhibits broad preference for phosphoinositides.
  Biochem J, 435, 597-608.  
21287624 V.Babin, C.Roland, and C.Sagui (2011).
The α-sheet: A missing-in-action secondary structure?
  Proteins, 79, 937-946.  
20667140 A.Lek, M.Lek, K.N.North, and S.T.Cooper (2010).
Phylogenetic analysis of ferlin genes reveals ancient eukaryotic origins.
  BMC Evol Biol, 10, 231.  
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.  
20734113 G.L.Butterfoss, E.F.DeRose, S.A.Gabel, L.Perera, J.M.Krahn, G.A.Mueller, X.Zheng, and R.E.London (2010).
Conformational dependence of 13C shielding and coupling constants for methionine methyl groups.
  J Biomol NMR, 48, 31-47.  
20735850 J.M.Moore-Dotson, J.B.Papke, and A.B.Harkins (2010).
Upregulation of synaptotagmin IV inhibits transmitter release in PC12 cells with targeted synaptotagmin I knockdown.
  BMC Neurosci, 11, 104.  
20440562 K.Schutters, and C.Reutelingsperger (2010).
Phosphatidylserine targeting for diagnosis and treatment of human diseases.
  Apoptosis, 15, 1072-1082.  
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.  
20956309 M.Segovia, E.Alés, M.A.Montes, I.Bonifas, I.Jemal, M.Lindau, A.Maximov, T.C.Südhof, and G.Alvarez de Toledo (2010).
Push-and-pull regulation of the fusion pore by synaptotagmin-7.
  Proc Natl Acad Sci U S A, 107, 19032-19037.  
  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
20826345 R.Guan, H.Dai, D.Han, S.C.Harrison, and T.Kirchhausen (2010).
Structure of the PTEN-like region of auxilin, a detector of clathrin-coated vesicle budding.
  Structure, 18, 1191-1198.
PDB code: 3n0a
20688915 Z.Wang, and E.R.Chapman (2010).
Rat and Drosophila synaptotagmin 4 have opposite effects during SNARE-catalyzed membrane fusion.
  J Biol Chem, 285, 30759-30766.  
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.  
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.  
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.  
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.  
19004828 N.A.Ramakrishnan, M.J.Drescher, and D.G.Drescher (2009).
Direct interaction of otoferlin with syntaxin 1A, SNAP-25, and the L-type voltage-gated calcium channel Cav1.3.
  J Biol Chem, 284, 1364-1372.  
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.  
19422675 N.Higuchi, K.Kohno, and T.Kadowaki (2009).
Specific retention of the protostome-specific PsGEF may parallel with the evolution of mushroom bodies in insect and lophotrochozoan brains.
  BMC Biol, 7, 21.  
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.  
  19008549 R.V.Stahelin (2009).
Lipid binding domains: more than simple lipid effectors.
  J Lipid Res, 50, S299-S304.  
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.  
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.  
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.  
18508081 E.Connell, A.Giniatullina, J.Lai-Kee-Him, R.Tavare, E.Ferrari, A.Roseman, D.Cojoc, A.R.Brisson, and B.Davletov (2008).
Cross-linking of phospholipid membranes is a conserved property of calcium-sensitive synaptotagmins.
  J Mol Biol, 380, 42-50.  
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.  
18784080 J.D.Gaffaney, F.M.Dunning, Z.Wang, E.Hui, and E.R.Chapman (2008).
Synaptotagmin C2B Domain Regulates Ca2+-triggered Fusion in Vitro: CRITICAL RESIDUES REVEALED BY SCANNING ALANINE MUTAGENESIS.
  J Biol Chem, 283, 31763-31775.  
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.  
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.  
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.  
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.  
17498067 R.Sagi-Eisenberg (2007).
The mast cell: where endocytosis and regulated exocytosis meet.
  Immunol Rev, 217, 292-303.  
17472963 R.V.Stahelin, P.Subramanian, M.Vora, W.Cho, and C.E.Chalfant (2007).
Ceramide-1-phosphate binds group IVA cytosolic phospholipase a2 via a novel site in the C2 domain.
  J Biol Chem, 282, 20467-20474.  
17478680 S.Martens, M.M.Kozlov, and H.T.McMahon (2007).
How synaptotagmin promotes membrane fusion.
  Science, 316, 1205-1208.  
17085504 S.Varma, and E.Jakobsson (2007).
The cPLA2 C2alpha domain in solution: structure and dynamics of its Ca2+-activated and cation-free states.
  Biophys J, 92, 966-976.  
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.  
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.  
16713576 B.DeLaBarre, J.C.Christianson, R.R.Kopito, and A.T.Brunger (2006).
Central pore residues mediate the p97/VCP activity required for ERAD.
  Mol Cell, 22, 451-462.  
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.  
17153918 H.J.Meijer, and F.Govers (2006).
Genomewide analysis of phospholipid signaling genes in Phytophthora spp.: novelties and a missing link.
  Mol Plant Microbe Interact, 19, 1337-1347.  
16616874 J.H.Hurley (2006).
Membrane binding domains.
  Biochim Biophys Acta, 1761, 805-811.  
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.  
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.  
16338929 L.Liu, X.Song, D.He, C.Komma, A.Kita, J.V.Virbasius, G.Huang, H.D.Bellamy, K.Miki, M.P.Czech, and G.W.Zhou (2006).
Crystal structure of the C2 domain of class II phosphatidylinositide 3-kinase C2alpha.
  J Biol Chem, 281, 4254-4260.
PDB code: 2b3r
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.  
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
  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.  
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.  
15778699 M.T.Madziva, J.Bai, A.Bhalla, E.R.Chapman, and J.M.Edwardson (2005).
Effects of synaptotagmin reveal two distinct mechanisms of agonist-stimulated internalization of the M4 muscarinic acetylcholine receptor.
  Br J Pharmacol, 144, 761-771.  
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.  
15994899 S.Málková, F.Long, R.V.Stahelin, S.V.Pingali, D.Murray, W.Cho, and M.L.Schlossman (2005).
X-ray reflectivity studies of cPLA2{alpha}-C2 domains adsorbed onto Langmuir monolayers of SOPC.
  Biophys J, 89, 1861-1873.  
15869386 W.Cho, and R.V.Stahelin (2005).
Membrane-protein interactions in cell signaling and membrane trafficking.
  Annu Rev Biophys Biomol Struct, 34, 119-151.  
16010732 X.Zhuang, Y.Xu, K.Chong, L.Lan, Y.Xue, and Z.Xu (2005).
OsAGAP, an ARF-GAP from rice, regulates root development mediated by auxin in Arabidopsis.
  Plant Cell Environ, 28, 147-156.  
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.  
14718912 B.Davletov, and J.L.Jiménez (2004).
Sculpting a domain by splicing.
  Nat Struct Mol Biol, 11, 4-5.  
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
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
13679516 J.H.Evans, S.H.Gerber, D.Murray, and C.C.Leslie (2004).
The calcium binding loops of the cytosolic phospholipase A2 C2 domain specify targeting to Golgi and ER in live cells.
  Mol Biol Cell, 15, 371-383.  
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.  
15105418 R.V.Stahelin, M.A.Digman, M.Medkova, B.Ananthanarayanan, J.D.Rafter, H.R.Melowic, and W.Cho (2004).
Mechanism of diacylglycerol-induced membrane targeting and activation of protein kinase Cdelta.
  J Biol Chem, 279, 29501-29512.  
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
12954613 B.Ananthanarayanan, R.V.Stahelin, M.A.Digman, and W.Cho (2003).
Activation mechanisms of conventional protein kinase C isoforms are determined by the ligand affinity and conformational flexibility of their C1 domains.
  J Biol Chem, 278, 46886-46894.  
14529272 C.Y.Kim, Y.D.Koo, J.B.Jin, B.C.Moon, C.H.Kang, S.T.Kim, B.O.Park, S.Y.Lee, M.L.Kim, I.Hwang, K.Y.Kang, J.D.Bahk, S.Y.Lee, and M.J.Cho (2003).
Rice C2-domain proteins are induced and translocated to the plasma membrane in response to a fungal elicitor.
  Biochemistry, 42, 11625-11633.  
12711617 E.M.Silinsky, and T.J.Searl (2003).
Phorbol esters and neurotransmitter release: more than just protein kinase C?
  Br J Pharmacol, 138, 1191-1201.  
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.  
12970180 M.Nishida, K.Sugimoto, Y.Hara, E.Mori, T.Morii, T.Kurosaki, and Y.Mori (2003).
Amplification of receptor signalling by Ca2+ entry-mediated translocation and activation of PLCgamma2 in B lymphocytes.
  EMBO J, 22, 4677-4688.  
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.  
14592859 R.A.Maselli, W.Books, and V.Dunne (2003).
Effect of inherited abnormalities of calcium regulation on human neuromuscular transmission.
  Ann N Y Acad Sci, 998, 18-28.  
12531893 R.V.Stahelin, J.D.Rafter, S.Das, and W.Cho (2003).
The molecular basis of differential subcellular localization of C2 domains of protein kinase C-alpha and group IVa cytosolic phospholipase A2.
  J Biol Chem, 278, 12452-12460.  
12710591 S.Barg (2003).
Mechanisms of exocytosis in insulin-secreting B-cells and glucagon-secreting A-cells.
  Pharmacol Toxicol, 92, 3.  
14529276 S.Corbalán-Garcia, S.Sánchez-Carrillo, J.García-García, and J.C.Gómez-Fernández (2003).
Characterization of the membrane binding mode of the C2 domain of PKC epsilon.
  Biochemistry, 42, 11661-11668.  
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.  
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.  
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.  
11884760 M.N.Teruel, and T.Meyer (2002).
Parallel single-cell monitoring of receptor-triggered membrane translocation of a calcium-sensing protein module.
  Science, 295, 1910-1912.  
12167630 T.Sklyarova, V.De Corte, K.Meerschaert, L.Devriendt, B.Vanloo, J.Bailey, L.J.Cook, M.Goethals, J.Van Damme, M.Puype, J.Vandekerckhove, and J.Gettemans (2002).
Fragmin60 encodes an actin-binding protein with a C2 domain and controls actin Thr-203 phosphorylation in Physarum plasmodia and sclerotia.
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Annexin V and phospholipid metabolism.
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An immunoglobulin-like fold in a major plant allergen: the solution structure of Phl p 2 from timothy grass pollen.
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Identification of a human cDNA clone that mediates adherence of pathogenic Neisseria to non-binding cells.
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The copines, a novel class of C2 domain-containing, calcium-dependent, phospholipid-binding proteins conserved from Paramecium to humans.
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Location of the membrane-docking face on the Ca2+-activated C2 domain of cytosolic phospholipase A2.
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Three-dimensional structure of an evolutionarily conserved N-terminal domain of syntaxin 1A.
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Mechanics of membrane fusion.
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Crystal structure of the phosphatidylethanolamine-binding protein from bovine brain: a novel structural class of phospholipid-binding proteins.
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RAB3 and synaptotagmin: the yin and yang of synaptic membrane fusion.
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Phospholipid-binding protein domains.
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Crystal structure of a calcium-phospholipid binding domain from cytosolic phospholipase A2.
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Structure of the protein kinase Cbeta phospholipid-binding C2 domain complexed with Ca2+.
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A conserved motif in the tail domain of vinculin mediates association with and insertion into acidic phospholipid bilayers.
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Photoinduced inactivation of protein kinase C by dequalinium identifies the RACK-1-binding domain as a recognition site.
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The C2 domains of Rabphilin3A specifically bind phosphatidylinositol 4,5-bisphosphate containing vesicles in a Ca2+-dependent manner. In vitro characteristics and possible significance.
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Synaptotagmin-1 is required for fibroblast growth factor-1 release.
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Solution structures of the Ca2+-free and Ca2+-bound C2A domain of synaptotagmin I: does Ca2+ induce a conformational change?
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Mechanism of phospholipid binding by the C2A-domain of synaptotagmin I.
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Lipid binding ridge on loops 2 and 3 of the C2A domain of synaptotagmin I as revealed by NMR spectroscopy.
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Properties and regulation of cytosolic phospholipase A2.
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Ca2+-signaling cycle of a membrane-docking C2 domain.
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Phosphoinositide binding specificity among phospholipase C isozymes as determined by photo-cross-linking to novel substrate and product analogs.
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DNA sequencing and analysis of 130 kb from yeast chromosome XV.
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Similarity between C2 domain jaws and immunoglobulin CDRs.
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Ca2+/calmodulin causes Rab3A to dissociate from synaptic membranes.
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A putative phosphatidylserine binding motif is not involved in the lipid regulation of protein kinase C.
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Protein kinase C and phospholipase C: bilayer interactions and regulation.
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A ternary metal binding site in the C2 domain of phosphoinositide-specific phospholipase C-delta1.
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PDB codes: 1djg 1djh 1dji
9232804 M.K.Bennett (1997).
Ca2+ and the regulation of neurotransmitter secretion.
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Protein kinase C: an example of a calcium-regulated protein binding to membranes (review).
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DOC2 proteins in rat brain: complementary distribution and proposed function as vesicular adapter proteins in early stages of secretion.
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The C2 domain of the ubiquitin protein ligase Nedd4 mediates Ca2+-dependent plasma membrane localization.
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Perforin is activated by a proteolytic cleavage during biosynthesis which reveals a phospholipid-binding C2 domain.
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Regulation of eukaryotic phosphatidylinositol-specific phospholipase C and phospholipase D.
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Synaptotagmin-syntaxin interaction: the C2 domain as a Ca2+-dependent electrostatic switch.
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Circular permutations of natural protein sequences: structural evidence.
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Isoform-specific, calcium-regulated interaction of the synaptic vesicle proteins SV2 and synaptotagmin.
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Extending the C2 domain family: C2s in PKCs delta, epsilon, eta, theta, phospholipases, GAPs, and perforin.
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The C2 domain calcium-binding motif: structural and functional diversity.
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Calcium-dependent switching of the specificity of phosphoinositide binding to synaptotagmin.
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C2 domain conformational changes in phospholipase C-delta 1.
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PDB codes: 1qas 1qat
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Mouse p170 is a novel phosphatidylinositol 3-kinase containing a C2 domain.
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The FSSP database: fold classification based on structure-structure alignment of proteins.
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Structural views of phosphoinositide-specific phospholipase C: signalling the way ahead.
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Annexins and protein kinases C.
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A predicted consensus structure for the protein kinase C2 homology (C2H) domain, the repeating unit of synaptotagmin.
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C2 region-derived peptides inhibit translocation and function of beta protein kinase C in vivo.
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Clostridial neurotoxins compromise the stability of a low energy SNARE complex mediating NSF activation of synaptic vesicle fusion.
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The protein kinase C and protein kinase C related gene families.
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Functional diversity of C2 domains of synaptotagmin family. Mutational analysis of inositol high polyphosphate binding domain.
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Mechanism of interaction of protein kinase C with phorbol esters. Reversibility and nature of membrane association.
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Mammalian homologues of Caenorhabditis elegans unc-13 gene define novel family of C2-domain proteins.
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The phospho-beta-galactosidase and synaptotagmin predictions.
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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.

 

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