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PDBsum entry 3kxx

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protein Protein-protein interface(s) links
Transferase PDB id
3kxx
Jmol
Contents
Protein chains
305 a.a. *
286 a.a. *
* Residue conservation analysis
PDB id:
3kxx
Name: Transferase
Title: Structure of the mutant fibroblast growth factor receptor 1
Structure: Basic fibroblast growth factor receptor 1. Chain: a, b, c, d. Fragment: kinase domain (unp residues 458 to 765). Synonym: fgfr-1, bfgf-r, fms-like tyrosine kinase 2, c-fgr. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: fgfr1, fgfbr, flg, flt2. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
3.20Å     R-factor:   0.222     R-free:   0.263
Authors: J.H.Bae,T.J.Boggon,F.Tome,V.Mandiyan,I.Lax,J.Schlessinger
Key ref:
J.H.Bae et al. (2010). Asymmetric receptor contact is required for tyrosine autophosphorylation of fibroblast growth factor receptor in living cells. Proc Natl Acad Sci U S A, 107, 2866-2871. PubMed id: 20133753 DOI: 10.1073/pnas.0914157107
Date:
04-Dec-09     Release date:   02-Mar-10    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P11362  (FGFR1_HUMAN) -  Fibroblast growth factor receptor 1
Seq:
Struc:
 
Seq:
Struc:
822 a.a.
305 a.a.*
Protein chains
Pfam   ArchSchema ?
P11362  (FGFR1_HUMAN) -  Fibroblast growth factor receptor 1
Seq:
Struc:
 
Seq:
Struc:
822 a.a.
286 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains A, B, C, D: 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!
  Biological process     signal transduction   5 terms 
  Biochemical function     transferase activity, transferring phosphorus-containing groups     6 terms  

 

 
    reference    
 
 
DOI no: 10.1073/pnas.0914157107 Proc Natl Acad Sci U S A 107:2866-2871 (2010)
PubMed id: 20133753  
 
 
Asymmetric receptor contact is required for tyrosine autophosphorylation of fibroblast growth factor receptor in living cells.
J.H.Bae, T.J.Boggon, F.Tomé, V.Mandiyan, I.Lax, J.Schlessinger.
 
  ABSTRACT  
 
Tyrosine autophosphorylation of receptor tyrosine kinases plays a critical role in regulation of kinase activity and in recruitment and activation of intracellular signaling pathways. Autophosphorylation is mediated by a sequential and precisely ordered intermolecular (trans) reaction. In this report we present structural and biochemical experiments demonstrating that formation of an asymmetric dimer between activated FGFR1 kinase domains is required for transphosphorylation of FGFR1 in FGF-stimulated cells. Transphosphorylation is mediated by specific asymmetric contacts between the N-lobe of one kinase molecule, which serves as an active enzyme, and specific docking sites on the C-lobe of a second kinase molecule, which serves a substrate. Pathological loss-of-function mutations or oncogenic activating mutations in this interface may hinder or facilitate asymmetric dimer formation and transphosphorylation, respectively. The experiments presented in this report provide the molecular basis underlying the control of transphosphorylation of FGF receptors and other receptor tyrosine kinases.
 
  Selected figure(s)  
 
Figure 1.
The overall structure of asymmetric activated FGFR1 kinase dimer and detailed views of inter receptor contacts. (A) Asymmetric dimer of active phosphorylated FGFR1 is shown in ribbon diagram. Molecules E and S of the asymmetric dimer are colored in cyan and green, respectively. (B) A detailed view of the interface formed between kinases in the asymmetric dimer. ATP analog (AMP-PCP) and interacting residues are shown in stick representation and the magnesium ion is shown as a blue sphere. Residues from molecule S are labeled with primes. The color scheme applied in this figure is used for all figures. Secondary structures are labeled in blue. (C) Surface representation of molecule E is depicted in cyan with interacting residues of the molecule S in stick and ribbon representation. Representative residues from molecule S are labeled. (D) Surface representation of molecule S is shown in green with interacting residues of molecule E (Pale Cyan) in stick and ribbon representation (www.pymol.org).
Figure 4.
The structures of kinase domains of (A) wt-FGFR1 (PDB ID: 3KY2), (B) FGFR1-RE mutant (PDB ID: 3KXX), and (C) activated FGFR1 (FGFR1-3P) (PDB ID: 3GQI) in a simplified cartoon (Upper) and in a ribbon diagram (Below). The catalytic loop is shown in yellow, and the activation loop in green, helix αC is depicted as a cylinder in the cartoon. Phosphotyrosines are colored in red in the cartoon and in stick representation in the ribbon diagram. (D) Ribbon diagrams of kinase insert loops of FGFR1, FGFR1-RE, and FGFR1-3P are in green, cyan, and blue, respectively. Side chains of R576, R577 and R577E are shown in stick representation. (E) Superposition of kinase insert regions of FGFR1 (Green), FGFR1-RE (Cyan), and FGFR1-3P (Blue) revealing multiple conformations of the kinase insert regions in the three structures.
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20432069 J.H.Bae, and J.Schlessinger (2010).
Asymmetric tyrosine kinase arrangements in activation or autophosphorylation of receptor tyrosine kinases.
  Mol Cells, 29, 443-448.  
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.