PDBsum entry 1tjm

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Endocytosis/exocytosis PDB id
Protein chain
157 a.a. *
Waters ×606
* Residue conservation analysis
PDB id:
Name: Endocytosis/exocytosis
Title: Crystallographic identification of sr2+ coordination site in synaptotagmin i c2b domain
Structure: Synaptotagmin i. Chain: a. Fragment: c2b domain. Synonym: syti, p65. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: syt1, syt. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
1.18Å     R-factor:   0.159     R-free:   0.174
Authors: Y.Cheng,S.M.Sequeira,L.Malinina,V.Tereshko,T.H.Sollner,D.J.P
Key ref:
Y.Cheng et al. (2004). Crystallographic identification of Ca2+ and Sr2+ coordination sites in synaptotagmin I C2B domain. Protein Sci, 13, 2665-2672. PubMed id: 15340165 DOI: 10.1110/ps.04832604
06-Jun-04     Release date:   28-Sep-04    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P21707  (SYT1_RAT) -  Synaptotagmin-1
421 a.a.
157 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 8 residue positions (black crosses)

 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: 10.1110/ps.04832604 Protein Sci 13:2665-2672 (2004)
PubMed id: 15340165  
Crystallographic identification of Ca2+ and Sr2+ coordination sites in synaptotagmin I C2B domain.
Y.Cheng, S.M.Sequeira, L.Malinina, V.Tereshko, T.H.Söllner, D.J.Patel.
Synaptotagmin I has two tandem Ca(2+)-binding C(2) domains, which are essential for fast synchronous synaptic transmission in the central nervous system. We have solved four crystal structures of the C(2)B domain, one of them in the cation-free form at 1.50 A resolution, two in the Ca(2+)-bound form at 1.04 A (two bound Ca(2+) ions) and 1.65 A (three bound Ca(2+) ions) resolution and one in the Sr(2+)-bound form at 1.18 A (one bound Sr(2+) ion) resolution. The side chains of four highly conserved aspartic acids (D303, D309, D363, and D365) and two main chain oxygens (M302:O and Y364:O), together with water molecules, are in direct contact with two bound Ca(2+) ions (sites 1 and 2). At higher Ca(2+) concentrations, the side chain of N333 rotates and cooperates with D309 to generate a third Ca(2+) coordination site (site 3). Divalent cation binding sites 1 and 2 in the C(2)B domain were previously identified from NMR NOE patterns and titration studies, supplemented by site-directed mutation analysis. One difference between the crystal and NMR studies involves D371, which is not involved in coordination with any of the identified Ca(2+) sites in the crystal structures, while it is coordinated to Ca(2+) in site 2 in the NMR structure. In the presence of Sr(2+), which is also capable of triggering exocytosis, but with lower efficiency, only one cation binding site (site 1) was occupied in the crystallographic structure.
  Selected figure(s)  
Figure 1.
Figure 1. Structure of C[2]B-B. (A) Front and side view of ribbon diagrams of the structure of C[2]B-B with 2 Ca^2+ ions. -Strands are labeled from 1 to 8, while helices are labeled H1 and H2. Ca^2+ ions are labeled Ca1 and Ca2. (B) Front and back view of electrostatic potential surface of C[2]B-B. The acidic and basic residues are colored green and orange, respectively.
Figure 3.
Figure 3. Cation-binding sites in (A) superpositioned C[2]B-NMR structures and (B) C[2]B-B, (C) C[2]B-C, and (D) C[2]B-D crystal structures. The Ca^2+ and Sr2+ ions are colored orange. The oxygen atoms that coordinate the cations are colored red. Water molecules are represented as small red spheres. Dashed lines indicate pentagonal bipyramidyl coordination to Ca^2+ sites (B,C) and tetragonal bipyramidyl coordination to Sr2+ site (D) in the crystal structures.
  The above figures are reprinted by permission from the Protein Society: Protein Sci (2004, 13, 2665-2672) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  20802832 M.Kirberger, X.Wang, K.Zhao, S.Tang, G.Chen, and J.J.Yang (2010).
Integration of Diverse Research Methods to Analyze and Engineer Ca-Binding Proteins: From Prediction to Production.
  Curr Bioinform, 5, 68-80.  
  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
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.  
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.  
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.  
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.  
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.  
  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
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.