NMR structure and mutagenesis of the N-terminal Dbl homology domain of the nucleotide exchange factor Trio

Cell. 1998 Oct 16;95(2):269-77. doi: 10.1016/s0092-8674(00)81757-2.

Abstract

Guanine nucleotide exchange factors for the Rho family of GTPases contain a Dbl homology (DH) domain responsible for catalysis and a pleckstrin homology (PH) domain whose function is unknown. Here we describe the solution structure of the N-terminal DH domain of Trio that catalyzes nucleotide exchange for Rac1. The all-alpha-helical protein has a very different structure compared to other exchange factors. Based on site-directed mutagenesis, functionally important residues of the DH domain were identified. They are all highly conserved and reside in close proximity on two a helices. In addition, we have discovered a unique capability of the PH domain to enhance nucleotide exchange in DH domain-containing proteins.

MeSH terms

  • Blood Proteins / chemistry
  • Blood Proteins / genetics
  • Guanine Nucleotide Exchange Factors*
  • Magnetic Resonance Spectroscopy
  • Molecular Sequence Data
  • Mutagenesis
  • Nucleotides / metabolism*
  • Phosphoproteins / chemistry*
  • Phosphoproteins / genetics*
  • Phosphoproteins / metabolism
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases / chemistry*
  • Protein-Serine-Threonine Kinases / genetics*
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins / genetics*
  • Sequence Homology, Amino Acid

Substances

  • Blood Proteins
  • Guanine Nucleotide Exchange Factors
  • Nucleotides
  • Phosphoproteins
  • Proto-Oncogene Proteins
  • platelet protein P47
  • Protein-Serine-Threonine Kinases
  • TRIO protein, human