Targeting proteins to membranes: structure of the signal recognition particle

Curr Opin Struct Biol. 2005 Apr;15(2):213-20. doi: 10.1016/


In all three kingdoms of life, co-translational targeting of secretory and membrane proteins to the prokaryotic plasma membrane or eukaryotic endoplasmic reticulum is mediated by a ribonucleoprotein complex, the signal recognition particle (SRP), and its membrane-associated receptor (SR). SRP binds to signal sequences of nascent proteins as they emerge from the exit tunnel of the ribosome. The resulting targeting complex, composed of the SRP and the ribosome-nascent chain complex (RNC), then docks with the SR in a GTP-dependent manner. Passing through a complex series of conformational states, SRP and SR deliver the RNC to the translocon, which in turn mediates protein translocation across or integration into the membrane. The core structural and mechanistic principles of SRP-dependent protein targeting are universally conserved. Recent structural investigations combining X-ray crystallography and cryo-electron microscopy have provided new insights into three essentials steps of the SRP-dependent protein targeting cycle: the assembly and interaction of the SRP ribonucleoprotein core, the GTP-dependent SRP-SR association, and the interaction between SRP and the ribosome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Archaeal Proteins / chemistry
  • Bacterial Proteins / chemistry
  • Binding Sites
  • Cell Membrane / chemistry*
  • Evolution, Molecular
  • Humans
  • Protein Binding
  • Protein Conformation
  • Protein Transport*
  • Receptors, Cytoplasmic and Nuclear / chemistry*
  • Receptors, Peptide / chemistry*
  • Signal Recognition Particle / chemistry*
  • Species Specificity
  • Structure-Activity Relationship


  • Archaeal Proteins
  • Bacterial Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Peptide
  • Signal Recognition Particle
  • signal peptide receptor