The many faces of Ras: recognition of small GTP-binding proteins

Trends Biochem Sci. 2001 Dec;26(12):710-6. doi: 10.1016/s0968-0004(01)01974-0.

Abstract

The structures of over 30 complexes of Ras superfamily small GTP-binding proteins bound to diverse protein partners have been reported. Comparison of these complexes using the sequences of the small GTP-binding proteins to align the contact sites shows that virtually all surface positions make contacts with at least one partner protein. Rather than highlighting a single consensus binding site, these comparisons illustrate the remarkable diversity of contacts of Ras superfamily members. Here, a new analysis technique, the interface array, is introduced to quantify patterns of surface contacts. The interface array shows that small GTP-binding proteins are recognized in at least nine distinct ways. Remarkably, binding partners with similar functions, including those with distinct folds, recognize small GTP-binding proteins in similar ways. These classes of shared surface contacts support the occurrence of both divergent and convergent evolutionary processes and suggest that specific effector functions require particular protein-protein contacts.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Binding Sites
  • Cluster Analysis
  • Consensus Sequence
  • Humans
  • Macromolecular Substances
  • Models, Molecular
  • Monomeric GTP-Binding Proteins / chemistry*
  • Monomeric GTP-Binding Proteins / genetics
  • Monomeric GTP-Binding Proteins / metabolism*
  • Protein Binding
  • Protein Conformation
  • Protein Interaction Mapping
  • Proto-Oncogene Proteins p21(ras) / chemistry
  • Proto-Oncogene Proteins p21(ras) / metabolism
  • Sequence Alignment

Substances

  • Macromolecular Substances
  • HRAS protein, human
  • Monomeric GTP-Binding Proteins
  • Proto-Oncogene Proteins p21(ras)