Crystal structure of the PI 3-kinase p85 amino-terminal SH2 domain and its phosphopeptide complexes

Nat Struct Biol. 1996 Apr;3(4):364-74. doi: 10.1038/nsb0496-364.


Crystal structures of the amino-terminal SH2 domain of the p85alpha subunit of phosphatidylinositol (PI) 3-kinase, alone and in complex with phosphopeptides bearing pTyr-Met/Val-Xaa-Met motifs, show that phosphopeptides bind in the two-pronged manner seen in high-affinity Lck and Src SH2 complexes, with conserved interactions between the domain and the peptide segment from phosphotyrosine to Met+3. Peptide binding requires the rearrangement of a tyrosyl side chain in the BG loop to create the hydrophobic Met+3 binding pocket. The structures suggest a mechanism for the biological specificity exhibited by PI 3-kinase in its interactions with phosphoprotein partners.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • Humans
  • Methionine / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Phosphatidylinositol 3-Kinases
  • Phosphopeptides / chemistry*
  • Phosphopeptides / metabolism
  • Phosphotransferases (Alcohol Group Acceptor) / chemistry*
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Protein Binding
  • Protein Conformation
  • Proto-Oncogene Proteins c-kit / chemistry
  • Receptors, Platelet-Derived Growth Factor / chemistry
  • src Homology Domains*


  • Phosphopeptides
  • Methionine
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor)
  • Proto-Oncogene Proteins c-kit
  • Receptors, Platelet-Derived Growth Factor