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PDBsum entry 2cjt
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protein ligands Protein-protein interface(s) links
Exocytosis PDB id
2cjt

 

 

 

 

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Contents
Protein chains
121 a.a.
127 a.a.
Ligands
EDO ×23
FMT ×11
Waters ×641
PDB id:
2cjt
Name: Exocytosis
Title: Structural basis for a munc13-1 homodimer - munc13-1 - rim heterodimer switch: c2-domains as versatile protein-protein interaction modules
Structure: Unc-13 homolog a. Chain: a, b, c, d. Fragment: c2a domain, residues 1-128. Synonym: munc13-1. Engineered: yes. Other_details: the recombinant protein contains residues 1-128 of munc13-1 and vector-derived sequences, ggv- at the n-terminus
Source: Rattus norvegicus. Rat. Organism_taxid: 10116. Expressed in: escherichia coli. Expression_system_taxid: 511693.
Biol. unit: Dimer (from PDB file)
Resolution:
1.44Å     R-factor:   0.160     R-free:   0.188
Authors: J.Lu,M.Machius,I.Dulubova,H.Dai,T.C.Sudhof,D.R.Tomchick,J.Rizo
Key ref: J.Lu et al. (2006). Structural basis for a Munc13-1 homodimer to Munc13-1/RIM heterodimer switch. Plos Biol, 4, e192. PubMed id: 16732694
Date:
06-Apr-06     Release date:   07-Jun-06    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q62768  (UN13A_RAT) -  Protein unc-13 homolog A from Rattus norvegicus
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1735 a.a.
121 a.a.
Protein chains
Pfam   ArchSchema ?
Q62768  (UN13A_RAT) -  Protein unc-13 homolog A from Rattus norvegicus
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1735 a.a.
127 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
Plos Biol 4:e192 (2006)
PubMed id: 16732694  
 
 
Structural basis for a Munc13-1 homodimer to Munc13-1/RIM heterodimer switch.
J.Lu, M.Machius, I.Dulubova, H.Dai, T.C.Südhof, D.R.Tomchick, J.Rizo.
 
  ABSTRACT  
 
C(2) domains are well characterized as Ca(2+)/phospholipid-binding modules, but little is known about how they mediate protein-protein interactions. In neurons, a Munc13-1 C(2)A-domain/RIM zinc-finger domain (ZF) heterodimer couples synaptic vesicle priming to presynaptic plasticity. We now show that the Munc13-1 C(2)A domain homodimerizes, and that homodimerization competes with Munc13-1/RIM heterodimerization. X-ray diffraction studies guided by nuclear magnetic resonance (NMR) experiments reveal the crystal structures of the Munc13-1 C(2)A-domain homodimer and the Munc13-1 C(2)A-domain/RIM ZF heterodimer at 1.44 A and 1.78 A resolution, respectively. The C(2)A domain adopts a beta-sandwich structure with a four-stranded concave side that mediates homodimerization, leading to the formation of an eight-stranded beta-barrel. In contrast, heterodimerization involves the bottom tip of the C(2)A-domain beta-sandwich and a C-terminal alpha-helical extension, which wrap around the RIM ZF domain. Our results describe the structural basis for a Munc13-1 homodimer-Munc13-1/RIM heterodimer switch that may be crucial for vesicle priming and presynaptic plasticity, uncovering at the same time an unexpected versatility of C(2) domains as protein-protein interaction modules, and illustrating the power of combining NMR spectroscopy and X-ray crystallography to study protein complexes.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21499244 C.Ma, W.Li, Y.Xu, and J.Rizo (2011).
Munc13 mediates the transition from the closed syntaxin-Munc18 complex to the SNARE complex.
  Nat Struct Mol Biol, 18, 542-549.  
21262469 L.Deng, P.S.Kaeser, W.Xu, and T.C.Südhof (2011).
RIM proteins activate vesicle priming by reversing autoinhibitory homodimerization of Munc13.
  Neuron, 69, 317-331.  
21318479 W.Feng, L.Pan, and M.Zhang (2011).
Combination of NMR spectroscopy and X-ray crystallography offers unique advantages for elucidation of the structural basis of protein complex assembly.
  Sci China Life Sci, 54, 101-111.  
  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
19528296 R.Nishihama, J.H.Schreiter, M.Onishi, E.A.Vallen, J.Hanna, K.Moravcevic, M.F.Lippincott, H.Han, M.A.Lemmon, J.R.Pringle, and E.Bi (2009).
Role of Inn1 and its interactions with Hof1 and Cyk3 in promoting cleavage furrow and septum formation in S. cerevisiae.
  J Cell Biol, 185, 995.  
17988208 C.W.Davis, and B.F.Dickey (2008).
Regulated airway goblet cell mucin secretion.
  Annu Rev Physiol, 70, 487-512.  
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.  
18200608 O.Okhrimenko, and I.Jelesarov (2008).
A survey of the year 2006 literature on applications of isothermal titration calorimetry.
  J Mol Recognit, 21, 1.  
17687497 C.Ma, H.Hou, W.Tian, and T.Xu (2007).
Expression, purification and characterization of critical domains of Munc13-1.
  Acta Biochim Biophys Sin (Shanghai), 39, 617-623.  
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
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.  
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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