Crystal structure of the Dbl and pleckstrin homology domains from the human Son of sevenless protein

Cell. 1998 Oct 16;95(2):259-68. doi: 10.1016/s0092-8674(00)81756-0.


Proteins containing Dbl homology (DH) domains activate Rho-family GTPases by functioning as specific guanine nucleotide exchange factors. All known DH domains have associated C-terminal pleckstrin homology (PH) domains that are implicated in targeting and regulatory functions. The crystal structure of a fragment of the human Son of sevenless protein containing the DH and PH domains has been determined at 2.3 A resolution. The entirely alpha-helical DH domain is unrelated in architecture to other nucleotide exchange factors. The active site of the DH domain, identified on the basis of sequence conservation and structural features, lies near the interface between the DH and PH domains. The structure suggests that ligation of the PH domain will be coupled structurally to the GTPase binding site.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites
  • Blood Proteins / chemistry*
  • Blood Proteins / genetics*
  • Crystallography
  • Guanine Nucleotide Exchange Factors
  • Humans
  • Molecular Sequence Data
  • Phosphoproteins*
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Proteins / chemistry*
  • Proteins / genetics*
  • Sequence Homology, Amino Acid


  • Blood Proteins
  • Guanine Nucleotide Exchange Factors
  • Phosphoproteins
  • Proteins
  • platelet protein P47

Associated data