Structural basis for the function of the beta subunit of the eukaryotic signal recognition particle receptor

Cell. 2003 Mar 21;112(6):793-803. doi: 10.1016/s0092-8674(03)00161-2.

Abstract

Protein translocation across and insertion into membranes is a process essential to all life forms. In higher eukaryotes, this process is initiated by targeting the translating ribosome to the endoplasmic reticulum via the signal recognition particle (SRP) and its membrane-associated heterodimeric receptor (SR). This targeting step is regulated by three G proteins, SRP54, SR alpha, and SR beta, which act in concert. Little is known about the regulatory role of SR beta. Here, we present the 1.7 A crystal structure of the SR beta-GTP subunit in complex with the interaction domain of SR alpha. Strikingly, the binding interface overlaps largely with the switch 1 region of SR beta. This finding, together with additional biochemical data, shows that the eukaryotic SR is a conditional and not an obligate heterodimer. The results suggest that the GTP/GDP switch cycle of SR beta functions as a regulatory switch for the receptor dimerization. We discuss the implications for the translocation pathway.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Conserved Sequence
  • Crystallography, X-Ray
  • Dimerization
  • Endoplasmic Reticulum / metabolism
  • Eukaryotic Cells
  • GTP-Binding Proteins / chemistry
  • GTP-Binding Proteins / metabolism
  • Guanosine Triphosphate / metabolism
  • Models, Molecular
  • Molecular Structure
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Protein Subunits / chemistry*
  • Protein Subunits / metabolism
  • Protein Transport
  • Receptors, Cytoplasmic and Nuclear / chemistry*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, Peptide / chemistry*
  • Receptors, Peptide / metabolism
  • Ribosomes / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Signal Recognition Particle / chemistry*
  • Signal Recognition Particle / genetics
  • Signal Recognition Particle / metabolism
  • Structure-Activity Relationship

Substances

  • Protein Subunits
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Peptide
  • Saccharomyces cerevisiae Proteins
  • Signal Recognition Particle
  • signal peptide receptor
  • Guanosine Triphosphate
  • GTP-Binding Proteins

Associated data

  • PDB/1NRJ