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PDBsum entry 2m20

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protein Protein-protein interface(s) links
Signaling protein PDB id
2m20
Jmol
Contents
Protein chain
60 a.a.
PDB id:
2m20
Name: Signaling protein
Title: Egfr transmembrane - juxtamembrane (tm-jm) segment in bicell guided nmr refined structure.
Structure: Epidermal growth factor receptor. Chain: a, b. Fragment: egfr transmembrane-juxtamembrane segment, unp res 697. Synonym: proto-oncogenE C-erbb-1, receptor tyrosine-protein erbb-1. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: egfr, erbb, erbb1, her1. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 10 models
Authors: N.F.Endres,R.Das,A.Smith,A.Arkhipov,E.Kovacs,Y.Huang,J.G.Pel Y.Shan,D.E.Shaw,D.E.Wemmer,J.T.Groves,J.Kuriyan
Key ref: N.F.Endres et al. (2013). Conformational coupling across the plasma membrane in activation of the EGF receptor. Cell, 152, 543-556. PubMed id: 23374349
Date:
11-Dec-12     Release date:   20-Feb-13    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
P00533  (EGFR_HUMAN) -  Epidermal growth factor receptor
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1210 a.a.
60 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 6 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: 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

 

 
    reference    
 
 
Cell 152:543-556 (2013)
PubMed id: 23374349  
 
 
Conformational coupling across the plasma membrane in activation of the EGF receptor.
N.F.Endres, R.Das, A.W.Smith, A.Arkhipov, E.Kovacs, Y.Huang, J.G.Pelton, Y.Shan, D.E.Shaw, D.E.Wemmer, J.T.Groves, J.Kuriyan.
 
  ABSTRACT  
 
How the epidermal growth factor receptor (EGFR) activates is incompletely understood. The intracellular portion of the receptor is intrinsically active in solution, and to study its regulation, we measured autophosphorylation as a function of EGFR surface density in cells. Without EGF, intact EGFR escapes inhibition only at high surface densities. Although the transmembrane helix and the intracellular module together suffice for constitutive activity even at low densities, the intracellular module is inactivated when tethered on its own to the plasma membrane, and fluorescence cross-correlation shows that it fails to dimerize. NMR and functional data indicate that activation requires an N-terminal interaction between the transmembrane helices, which promotes an antiparallel interaction between juxtamembrane segments and release of inhibition by the membrane. We conclude that EGF binding removes steric constraints in the extracellular module, promoting activation through N-terminal association of the transmembrane helices.