Structure of a Ran-binding domain complexed with Ran bound to a GTP analogue: implications for nuclear transport

Nature. 1999 Mar 4;398(6722):39-46. doi: 10.1038/17969.

Abstract

The protein Ran is a small GTP-binding protein that binds to two types of effector inside the cell: Ran-binding proteins, which have a role in terminating export processes from the nucleus to the cytoplasm, and importin-beta-like molecules that bind cargo proteins during nuclear transport. The Ran-binding domain is a conserved sequence motif found in several proteins that participate in these transport processes. The Ran-binding protein RanBP2 contains four of these domains and constitutes a large part of the cytoplasmic fibrils that extend from the nuclear-pore complex. The structure of Ran bound to a non-hydrolysable GTP analogue (Ran x GppNHp) in complex with the first Ran-binding domain (RanBD1) of human RanBP2 reveals not only that RanBD1 has a pleckstrin-homology domain fold, but also that the switch-I region of Ran x GppNHp resembles the canonical Ras GppNHp structure and that the carboxy terminus of Ran is wrapped around RanBD1, contacting a basic patch on RanBD1 through its acidic end. This molecular 'embrace' enables RanBDs to sequester the Ran carboxy terminus, triggering the dissociation of Ran x GTP from importin-beta-related transport factors and facilitating GTP hydrolysis by the GTPase-activating protein ranGAP. Such a mechanism represents a new type of switch mechanism and regulatory protein-protein interaction for a Ras-related protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Biological Transport
  • Blood Proteins / chemistry
  • Cell Nucleus / metabolism*
  • Conserved Sequence
  • Crystallography, X-Ray
  • Cytoplasm / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Escherichia coli
  • GTP-Binding Proteins / chemistry
  • GTP-Binding Proteins / metabolism*
  • Guanylyl Imidodiphosphate / chemistry
  • Guanylyl Imidodiphosphate / metabolism*
  • Humans
  • Models, Molecular
  • Molecular Chaperones
  • Molecular Sequence Data
  • Nuclear Pore Complex Proteins*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Phosphoproteins*
  • Phosphotyrosine / metabolism
  • Protein Binding
  • Protein Conformation
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Homology, Amino Acid
  • ran GTP-Binding Protein

Substances

  • Blood Proteins
  • DNA-Binding Proteins
  • Molecular Chaperones
  • Nuclear Pore Complex Proteins
  • Nuclear Proteins
  • Phosphoproteins
  • Recombinant Fusion Proteins
  • platelet protein P47
  • ran-binding protein 2
  • Phosphotyrosine
  • Guanylyl Imidodiphosphate
  • GTP-Binding Proteins
  • ran GTP-Binding Protein

Associated data

  • PDB/1RRP