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PDBsum entry 1l4a
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protein Protein-protein interface(s) links
Endocytosis/exocytosis PDB id
1l4a

 

 

 

 

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Contents
Protein chains
66 a.a. *
82 a.a. *
73 a.a. *
75 a.a. *
28 a.a. *
Waters ×23
* Residue conservation analysis
PDB id:
1l4a
Name: Endocytosis/exocytosis
Title: X-ray structure of the neuronal complexin/snare complex from the squid loligo pealei
Structure: Synaptobrevin. Chain: a. Engineered: yes. S-syntaxin. Chain: b. Engineered: yes. S-snap25 fusion protein. Chain: c. Engineered: yes.
Source: Loligo pealei. Organism_taxid: 6621. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Pentamer (from PQS)
Resolution:
2.95Å     R-factor:   0.297     R-free:   0.345
Authors: A.Bracher,J.Kadlec,H.Betz,W.Weissenhorn
Key ref:
A.Bracher et al. (2002). X-ray structure of a neuronal complexin-SNARE complex from squid. J Biol Chem, 277, 26517-26523. PubMed id: 12004067 DOI: 10.1074/jbc.M203460200
Date:
04-Mar-02     Release date:   31-Jul-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P47194  (SYB_DORPE) -  Synaptobrevin from Doryteuthis pealeii
Seq:
Struc: 		125 a.a.
66 a.a.
Protein chain
Pfam   ArchSchema ?
O46345  (O46345_DORPE) -  S-syntaxin from Doryteuthis pealeii
Seq:
Struc: 		292 a.a.
82 a.a.*
Protein chain
Pfam   ArchSchema ?
Q8T3S4  (Q8T3S4_DORPE) -  Synaptosomal-associated protein from Doryteuthis pealeii
Seq:
Struc: 		212 a.a.
73 a.a.
Protein chain
Pfam   ArchSchema ?
Q8T3S4  (Q8T3S4_DORPE) -  Synaptosomal-associated protein from Doryteuthis pealeii
Seq:
Struc: 		212 a.a.
75 a.a.
Protein chain
Pfam   ArchSchema ?
Q95PA1  (CPLX_DORPE) -  Complexin from Doryteuthis pealeii
Seq:
Struc: 		152 a.a.
28 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 5 residue positions (black crosses)

 

 
DOI no: 10.1074/jbc.M203460200 J Biol Chem 277:26517-26523 (2002)
PubMed id: 12004067  
 
 
X-ray structure of a neuronal complexin-SNARE complex from squid.
A.Bracher, J.Kadlec, H.Betz, W.Weissenhorn.
 
  ABSTRACT  
 
Nerve terminals release neurotransmitters from vesicles into the synaptic cleft upon transient increases in intracellular Ca(2+). This exocytotic process requires the formation of trans SNARE complexes and is regulated by accessory proteins including the complexins. Here we report the crystal structure of a squid core complexin-SNARE complex at 2.95-A resolution. A helical segment of complexin binds in anti-parallel fashion to the four-helix bundle of the core SNARE complex and interacts at its C terminus with syntaxin and synaptobrevin around the ionic zero layer of the SNARE complex. We propose that this structure is part of a multiprotein fusion machinery that regulates vesicle fusion at a late pre-fusion stage. Accordingly, Ca(2+) may initiate membrane fusion by acting directly or indirectly on complexin, thus allowing the conformational transitions of the trans SNARE complex that are thought to drive membrane fusion.
 
  Selected figure(s)  
 
Figure 2.
Fig. 2. a, alignment of squid SNARE sequences from Sb , Sx, Sn1, and Sn2, present in the crystal structure, and their respective rat SNARE complex sequences. The positions of heptad repeat layers are indicated based on the rat SNARE complex structure (7) and our squid SNARE complex structure. The residues contacting cpx are marked with asterisks. Sequence identities between rat and squid chains are 91% for Sb, 87% for Sx, 79% for Sn1, and 68% for Sn2 considering only the SNARE motifs (layers 7 to +8). Hydrophobic layers are highlighted in gray, and the numbering is according to the squid sequences. b, sequence alignment of rat cpx I and II and squid cpx. The residues present in the structure are shown, and the construct used in crystallization is indicated as dashed lines. Residues contacting Sx and Sb are marked with asterisks. Identical residues are highlighted in black boxes, and similar residues are shaded in gray. The numbering is according to the squid sequence. 		Figure 3.
Fig. 3. cpx interacts with the SNARE protein chains Sb and Sx between layers 3 and +1. Close-up views of the three major cross sections of cpx·SNARE complex interactions. For clarity, only hydrophobic layer residues and contact residues are shown. Polar interactions are indicated as dashed lines. a, cross-section of hydrophilic and hydrophobic interactions at layer 3. Complexin Tyr-73 packs anti-clockwise against Sx Met-218 and Sb Arg-56 following the classical "knobs into holes" arrangement. b, cross-section of predominately hydrophobic interactions at layer 1. Note that the cpx helix is closer to the Sb helix than to the Sx helix, and the packing deviates from the "knobs into holes" arrangement. c, cross-section of interactions at the ionic 0 layer, which are mostly hydrophilic. The hydrogen bond distances are indicated for the SNARE residues.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 26517-26523) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
23060190 R.Jahn, and D.Fasshauer (2012).
Molecular machines governing exocytosis of synaptic vesicles.
  Nature, 490, 201-207.  
21215634 J.A.Martin, Z.Hu, K.M.Fenz, J.Fernandez, and J.S.Dittman (2011).
Complexin has opposite effects on two modes of synaptic vesicle fusion.
  Curr Biol, 21, 97.  
20400951 M.Xue, T.K.Craig, J.Xu, H.T.Chao, J.Rizo, and C.Rosenmund (2010).
Binding of the complexin N terminus to the SNARE complex potentiates synaptic-vesicle fusogenicity.
  Nat Struct Mol Biol, 17, 568-575.  
20383135 S.J.An, C.P.Grabner, and D.Zenisek (2010).
Real-time visualization of complexin during single exocytic events.
  Nat Neurosci, 13, 577-583.  
19164751 A.Maximov, J.Tang, X.Yang, Z.P.Pang, and T.C.Südhof (2009).
Complexin controls the force transfer from SNARE complexes to membranes in fusion.
  Science, 323, 516-521.  
19914176 A.Stein, and R.Jahn (2009).
Complexins living up to their name--new light on their role in exocytosis.
  Neuron, 64, 295-297.  
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.  
19164750 C.G.Giraudo, A.Garcia-Diaz, W.S.Eng, Y.Chen, W.A.Hendrickson, T.J.Melia, and J.E.Rothman (2009).
Alternative zippering as an on-off switch for SNARE-mediated fusion.
  Science, 323, 512-516.  
19914185 M.Xue, Y.Q.Lin, H.Pan, K.Reim, H.Deng, H.J.Bellen, and C.Rosenmund (2009).
Tilting the balance between facilitatory and inhibitory functions of mammalian and Drosophila Complexins orchestrates synaptic vesicle exocytosis.
  Neuron, 64, 367-380.  
19762473 U.Winter, X.Chen, and D.Fasshauer (2009).
A conserved membrane attachment site in alpha-SNAP facilitates N-ethylmaleimide-sensitive factor (NSF)-driven SNARE complex disassembly.
  J Biol Chem, 284, 31817-31826.  
19301366 Y.Brunner, D.Schvartz, Y.Couté, and J.C.Sanchez (2009).
Proteomics of regulated secretory organelles.
  Mass Spectrom Rev, 28, 844-867.  
18499660 C.G.Giraudo, A.Garcia-Diaz, W.S.Eng, A.Yamamoto, T.J.Melia, and J.E.Rothman (2008).
Distinct domains of complexins bind SNARE complexes and clamp fusion in vitro.
  J Biol Chem, 283, 21211-21219.  
19132534 H.Tokumaru, C.Shimizu-Okabe, and T.Abe (2008).
Direct interaction of SNARE complex binding protein synaphin/complexin with calcium sensor synaptotagmin 1.
  Brain Cell Biol, 36, 173-189.  
18275821 K.Weninger, M.E.Bowen, U.B.Choi, S.Chu, and A.T.Brunger (2008).
Accessory proteins stabilize the acceptor complex for synaptobrevin, the 1:1 syntaxin/SNAP-25 complex.
  Structure, 16, 308-320.  
18445121 N.Brose (2008).
For better or for worse: complexins regulate SNARE function and vesicle fusion.
  Traffic, 9, 1403-1413.  
17767192 C.M.Carr, and M.Munson (2007).
Tag team action at the synapse.
  EMBO Rep, 8, 834-838.  
17828276 M.Xue, K.Reim, X.Chen, H.T.Chao, H.Deng, J.Rizo, N.Brose, and C.Rosenmund (2007).
Distinct domains of complexin I differentially regulate neurotransmitter release.
  Nat Struct Mol Biol, 14, 949-958.  
17513363 Y.Li, G.J.Augustine, and K.Weninger (2007).
Kinetics of complexin binding to the SNARE complex: correcting single molecule FRET measurements for hidden events.
  Biophys J, 93, 2178-2187.  
16845390 J.R.Schaub, X.Lu, B.Doneske, Y.K.Shin, and J.A.McNew (2006).
Hemifusion arrest by complexin is relieved by Ca2+-synaptotagmin I.
  Nat Struct Mol Biol, 13, 748-750.  
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.  
17312998 K.Chen, X.Huang, Z.Bao, and H.Gaisano (2006).
Characterization of VAMP-2 gene from marine teleostean, Lateolabrax japonicus.
  Sci China C Life Sci, 49, 591-596.  
16819626 U.Becherer, and J.Rettig (2006).
Vesicle pools, docking, priming, and release.
  Cell Tissue Res, 326, 393-407.  
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.  
15113421 A.Bracher, and W.Weissenhorn (2004).
Crystal structure of the Habc domain of neuronal syntaxin from the squid Loligo pealei reveals conformational plasticity at its C-terminus.
  BMC Struct Biol, 4, 6.
PDB code: 1s94
15464884 S.An, and D.Zenisek (2004).
Regulation of exocytosis in neurons and neuroendocrine cells.
  Curr Opin Neurobiol, 14, 522-530.  
12426383 A.Bracher, and W.Weissenhorn (2002).
Structural basis for the Golgi membrane recruitment of Sly1p by Sed5p.
  EMBO J, 21, 6114-6124.
PDB code: 1mqs
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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