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PDBsum entry 1y8f
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protein metals links
Endocytosis/exocytosis,signaling protein PDB id
1y8f

 

 

 

 

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Contents
Protein chain
51 a.a. *
Metals
_ZN ×2
* Residue conservation analysis
PDB id:
1y8f
Name: Endocytosis/exocytosis,signaling protein
Title: Solution structure of the munc13-1 c1-domain
Structure: Unc-13 homolog a. Chain: a. Fragment: c1-domain (residues 567-616). Synonym: munc13-1. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: munc13-1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
NMR struc: 20 models
Authors: N.Shen,O.Guryev,J.Rizo
Key ref:
N.Shen et al. (2005). Intramolecular occlusion of the diacylglycerol-binding site in the C1 domain of munc13-1. Biochemistry, 44, 1089-1096. PubMed id: 15667202 DOI: 10.1021/bi0476127
Date:
12-Dec-04     Release date:   12-Apr-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q62768  (UN13A_RAT) -  Protein unc-13 homolog A from Rattus norvegicus
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1735 a.a.
51 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 

 
DOI no: 10.1021/bi0476127 Biochemistry 44:1089-1096 (2005)
PubMed id: 15667202  
 
 
Intramolecular occlusion of the diacylglycerol-binding site in the C1 domain of munc13-1.
N.Shen, O.Guryev, J.Rizo.
 
  ABSTRACT  
 
Protein kinase C (PKC) isozymes and other receptors of diacylglycerol (DAG) bind to this widespread second messenger through their C(1) domains. These alternative DAG receptors include munc13-1, a large neuronal protein that is crucial for DAG-dependent augmentation of neurotransmitter release. Whereas the structures of several PKC C(1) domains have been determined and have been shown to require little conformational changes for ligand binding, it is unclear whether the C(1) domains from other DAG receptors contain specific structural features with key functional significance. To gain insight into this question, we have determined the three-dimensional structure in solution of the munc13-1 C(1) domain using NMR spectroscopy. The overall structure includes two beta-sheets, a short C-terminal alpha-helix, and two Zn(2+)-binding sites, resembling the structures of PKC C(1) domains. However, the munc13-1 C(1) domain exhibits striking structural differences with the PKC C(1) domains in the ligand-binding site. These differences result in occlusion of the binding site of the munc13-1 C(1) domain by a conserved tryptophan side chain that in PKCs adopts a completely different orientation. As a consequence, the munc13-1 C(1) domain requires a considerable conformational change for ligand binding. This structural distinction is expected to decrease the DAG affinity of munc13-1 compared to that of PKCs, and is likely to be critical for munc13-1 function. On the basis of these results, we propose that augmentation of neurotransmitter release may be activated at higher DAG levels than PKCs as a potential mechanism for uncoupling augmentation of release from the multitude of other signaling processes mediated by DAG.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21419781 M.D.Stewart, B.Morgan, F.Massi, and T.I.Igumenova (2011).
Probing the determinants of diacylglycerol binding affinity in the C1B domain of protein kinase Cα.
  J Mol Biol, 408, 949-970.  
18826946 F.Colón-González, F.C.Leskow, and M.G.Kazanietz (2008).
Identification of an autoinhibitory mechanism that restricts C1 domain-mediated activation of the Rac-GAP alpha2-chimaerin.
  J Biol Chem, 283, 35247-35257.  
18707088 S.El Kazzouli, N.E.Lewin, P.M.Blumberg, and V.E.Marquez (2008).
Conformationally constrained analogues of diacylglycerol. 30. An investigation of diacylglycerol-lactones containing heteroaryl groups reveals compounds with high selectivity for Ras guanyl nucleotide-releasing proteins.
  J Med Chem, 51, 5371-5386.  
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.  
17071619 D.R.Dries, L.L.Gallegos, and A.C.Newton (2007).
A single residue in the C1 domain sensitizes novel protein kinase C isoforms to cellular diacylglycerol production.
  J Biol Chem, 282, 826-830.  
18043066 L.B.Metz, N.Dasgupta, C.Liu, S.J.Hunt, and C.M.Crowder (2007).
An evolutionarily conserved presynaptic protein is required for isoflurane sensitivity in Caenorhabditis elegans.
  Anesthesiology, 107, 971-982.  
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
16943444 J.Das, X.Zhou, and K.W.Miller (2006).
Identification of an alcohol binding site in the first cysteine-rich domain of protein kinase Cdelta.
  Protein Sci, 15, 2107-2119.  
16079140 R.V.Stahelin, J.Wang, N.R.Blatner, J.D.Rafter, D.Murray, and W.Cho (2005).
The origin of C1A-C2 interdomain interactions in protein kinase Calpha.
  J Biol Chem, 280, 36452-36463.  
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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