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PDBsum entry 3bu3

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protein Protein-protein interface(s) links
Transferase PDB id
3bu3
Jmol
Contents
Protein chains
297 a.a. *
14 a.a. *
Waters ×267
* Residue conservation analysis
PDB id:
3bu3
Name: Transferase
Title: Crystal structure of the insulin receptor kinase in complex with irs2 krlb peptide
Structure: Insulin receptor subunit beta. Chain: a. Fragment: protein kinase. Synonym: ir, cd220 antigen. Engineered: yes. Insulin receptor substrate 2. Chain: b. Fragment: unp residues 620-634. Synonym: irs-2, 4ps.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: insr. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Synthetic: yes. Other_details: the sequence of this peptide natually exists in mus musculus.
Resolution:
1.65Å     R-factor:   0.203     R-free:   0.220
Authors: J.Wu,S.R.Hubbard
Key ref:
J.Wu et al. (2008). Structural and biochemical characterization of the KRLB region in insulin receptor substrate-2. Nat Struct Mol Biol, 15, 251-258. PubMed id: 18278056 DOI: 10.1038/nsmb.1388
Date:
31-Dec-07     Release date:   19-Feb-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P06213  (INSR_HUMAN) -  Insulin receptor
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1382 a.a.
297 a.a.*
Protein chain
Pfam   ArchSchema ?
P81122  (IRS2_MOUSE) -  Insulin receptor substrate 2
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1321 a.a.
14 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: Chain A: E.C.2.7.10.1  - Receptor protein-tyrosine kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
ATP
+ [protein]-L-tyrosine
= ADP
+ [protein]-L-tyrosine phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   1 term 
  Biological process     transmembrane receptor protein tyrosine kinase signaling pathway   2 terms 
  Biochemical function     transferase activity, transferring phosphorus-containing groups     5 terms  

 

 
    reference    
 
 
DOI no: 10.1038/nsmb.1388 Nat Struct Mol Biol 15:251-258 (2008)
PubMed id: 18278056  
 
 
Structural and biochemical characterization of the KRLB region in insulin receptor substrate-2.
J.Wu, Y.D.Tseng, C.F.Xu, T.A.Neubert, M.F.White, S.R.Hubbard.
 
  ABSTRACT  
 
Insulin receptor substrates 1 and 2 (IRS1 and -2) are crucial adaptor proteins in mediating the metabolic and mitogenic effects of insulin and insulin-like growth factor 1. These proteins consist of a pleckstrin homology domain, a phosphotyrosine binding domain and a C-terminal region containing numerous sites of tyrosine, serine and threonine phosphorylation. Previous yeast two-hybrid studies identified a region unique to IRS2, termed the kinase regulatory-loop binding (KRLB) region, which interacts with the tyrosine kinase domain of the insulin receptor. Here we present the crystal structure of the insulin receptor kinase in complex with a 15-residue peptide from the KRLB region. In the structure, this segment of IRS2 is bound in the kinase active site with Tyr628 positioned for phosphorylation. Although Tyr628 was phosphorylated by the insulin receptor, its catalytic turnover was poor, resulting in kinase inhibition. Our studies indicate that the KRLB region functions to limit tyrosine phosphorylation of IRS2.
 
  Selected figure(s)  
 
Figure 1.
Domain organization and location of tyrosine-phosphorylation sites are drawn to linear scale (mouse numbering, 1,321 residues). Tyrosine-phosphorylation sites that are recruitment sites for PI3K (Y XM motif) are labeled by ^*, the GRB2 site (Y911) is labeled by † and the two SHP2 sites (Y1242 and Y1303) are labeled by §. The KRLB region as determined by Y2H studies (residues 591–733) is shown with dashed lines, and the 15-residue region that was cocrystallized with IRK is shown in the gray box, with the sequence expanded below and Tyr628 underlined. The corresponding 15-residue sequence in IRS1 (mouse) is also shown.
Figure 2.
(a) IRK is shown as a molecular surface, with the N lobe colored dark gray and the C lobe colored light gray. The activation loop (residues 1150–1171) is colored green and the catalytic loop (residues 1130–1137) is colored orange. IRS2 KRLB^Y628 is shown in stick representation. The final 2F[o] - F[c] electron density (1.65-Å resolution, 1 contour) is shown in blue mesh. The N and C termini of the peptide are labeled.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2008, 15, 251-258) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20883498 T.Brummer, C.Schmitz-Peiffer, and R.J.Daly (2010).
Docking proteins.
  FEBS J, 277, 4356-4369.  
20638297 Z.Cheng, Y.Tseng, and M.F.White (2010).
Insulin signaling meets mitochondria in metabolism.
  Trends Endocrinol Metab, 21, 589-598.  
19333572 A.Krook, and J.R.Zierath (2009).
Specificity of insulin signalling in human skeletal muscle as revealed by small interfering RNA.
  Diabetologia, 52, 1231-1239.  
18319738 S.Y.Park, and S.E.Shoelson (2008).
When a domain is not a domain.
  Nat Struct Mol Biol, 15, 224-226.  
18590693 X.C.Dong, K.D.Copps, S.Guo, Y.Li, R.Kollipara, R.A.DePinho, and M.F.White (2008).
Inactivation of hepatic Foxo1 by insulin signaling is required for adaptive nutrient homeostasis and endocrine growth regulation.
  Cell Metab, 8, 65-76.  
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.