Crystal structures of Ral-GppNHp and Ral-GDP reveal two binding sites that are also present in Ras and Rap

Structure. 2004 Nov;12(11):2025-36. doi: 10.1016/j.str.2004.08.011.

Abstract

RalA is a GTPase with effectors such as Sec5 and Exo84 in the exocyst complex and RalBP1, a GAP for Rho proteins. We report the crystal structures of Ral-GppNHp and Ral-GDP. Disordered switch I and switch II, located away from crystal contacts, are observed in one of the molecules in the asymmetric unit of the Ral-GppNHp structure. In the other molecule in the asymmetric unit, a second Mg(2+) ion is bound to the GppNHp gamma-phosphate in an environment in which switch I is pulled away from the nucleotide and switch II is found in a tight beta turn. Clustering of conserved residues on the surface of Ral-GppNHp identifies two putative sites for protein-protein interaction. One site is adjacent to switch I. The other is modulated by switch II and is obstructed in Ral-GDP. The Ral structures are discussed in the context of the published structures of the Ral/Sec5 complex, Ras, and Rap.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Catalytic Domain
  • Crystallography, X-Ray
  • Guanosine Diphosphate / chemistry*
  • Guanosine Diphosphate / metabolism
  • Guanosine Triphosphate / analogs & derivatives
  • Guanosine Triphosphate / chemistry*
  • Guanosine Triphosphate / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Sequence Homology, Amino Acid
  • rap GTP-Binding Proteins / chemistry*
  • rap GTP-Binding Proteins / metabolism
  • ras Proteins / chemistry*
  • ras Proteins / metabolism

Substances

  • Guanosine Diphosphate
  • Guanosine Triphosphate
  • rap GTP-Binding Proteins
  • ras Proteins

Associated data

  • PDB/1U8Y
  • PDB/1U8Z
  • PDB/1U9O