PDBsum entry 3loh

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protein Protein-protein interface(s) links
Immune system/hormone receptor PDB id
Protein chains
215 a.a. *
219 a.a. *
193 a.a. *
214 a.a. *
825 a.a. *
* Residue conservation analysis
PDB id:
Name: Immune system/hormone receptor
Title: Structure of the insulin receptor ectodomain, including ct p
Structure: Fab 83-7 heavy chain. Chain: a. Engineered: yes. Fab 83-7 light chain. Chain: b. Engineered: yes. Fab 83-14 heavy chain. Chain: c. Engineered: yes.
Source: Mus musculus. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562. Homo sapiens. Human. Organism_taxid: 9606. Gene: insr. Expressed in: cricetulus griseus.
3.80Å     R-factor:   0.228     R-free:   0.285
Authors: M.C.Lawrence,B.J.Smith
Key ref: B.J.Smith et al. (2010). Structural resolution of a tandem hormone-binding element in the insulin receptor and its implications for design of peptide agonists. Proc Natl Acad Sci U S A, 107, 6771-6776. PubMed id: 20348418
03-Feb-10     Release date:   28-Apr-10    
Go to PROCHECK summary

Protein chain
No UniProt id for this chain
Struc: 215 a.a.
Protein chain
No UniProt id for this chain
Struc: 219 a.a.
Protein chain
No UniProt id for this chain
Struc: 193 a.a.
Protein chain
No UniProt id for this chain
Struc: 214 a.a.
Protein chain
Pfam   ArchSchema ?
P06213  (INSR_HUMAN) -  Insulin receptor
1382 a.a.
825 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chain E: E.C.  - Receptor protein-tyrosine kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
+ [protein]-L-tyrosine
+ [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     ATP binding     2 terms  


Proc Natl Acad Sci U S A 107:6771-6776 (2010)
PubMed id: 20348418  
Structural resolution of a tandem hormone-binding element in the insulin receptor and its implications for design of peptide agonists.
B.J.Smith, K.Huang, G.Kong, S.J.Chan, S.Nakagawa, J.G.Menting, S.Q.Hu, J.Whittaker, D.F.Steiner, P.G.Katsoyannis, C.W.Ward, M.A.Weiss, M.C.Lawrence.
The C-terminal segment of the human insulin receptor alpha-chain (designated alphaCT) is critical to insulin binding as has been previously demonstrated by alanine scanning mutagenesis and photo-cross-linking. To date no information regarding the structure of this segment within the receptor has been available. We employ here the technique of thermal-factor sharpening to enhance the interpretability of the electron-density maps associated with the earlier crystal structure of the human insulin receptor ectodomain. The alphaCT segment is now resolved as being engaged with the central beta-sheet of the first leucine-rich repeat (L1) domain of the receptor. The segment is alpha-helical in conformation and extends 11 residues N-terminal of the classical alphaCT segment boundary originally defined by peptide mapping. This tandem structural element (alphaCT-L1) thus defines the intact primary insulin-binding surface of the apo-receptor. The structure, together with isothermal titration calorimetry data of mutant alphaCT peptides binding to an insulin minireceptor, leads to the conclusion that putative "insulin-mimetic" peptides in the literature act at least in part as mimics of the alphaCT segment as well as of insulin. Photo-cross-linking by novel bifunctional insulin derivatives demonstrates that the interaction of insulin with the alphaCT segment and the L1 domain occurs in trans, i.e., these components of the primary binding site are contributed by alternate alpha-chains within the insulin receptor homodimer. The tandem structural element defines a new target for the design of insulin agonists for the treatment of diabetes mellitus.

Literature references that cite this PDB file's key reference

  PubMed id Reference
23302862 J.G.Menting, J.Whittaker, M.B.Margetts, L.J.Whittaker, G.K.Kong, B.J.Smith, C.J.Watson, L.Záková, E.Kletvíková, J.Jiráček, S.J.Chan, D.F.Steiner, G.G.Dodson, A.M.Brzozowski, M.A.Weiss, C.W.Ward, and M.C.Lawrence (2013).
How insulin engages its primary binding site on the insulin receptor.
  Nature, 493, 241-245.
PDB codes: 3w11 3w12 3w13 3w14
21318406 E.Raffan, M.A.Soos, N.Rocha, A.Tuthill, A.R.Thomsen, C.S.Hyden, J.W.Gregory, P.Hindmarsh, M.Dattani, E.Cochran, J.Al Kaabi, P.Gorden, I.Barroso, N.Morling, S.O'Rahilly, and R.K.Semple (2011).
Founder effect in the Horn of Africa for an insulin receptor mutation that may impair receptor recycling.
  Diabetologia, 54, 1057-1065.  
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 codes are shown on the right.