Structure of a prehandover mammalian ribosomal SRP·SRP receptor targeting complex

Science. 2018 Apr 20;360(6386):323-327. doi: 10.1126/science.aar7924. Epub 2018 Mar 22.


Signal recognition particle (SRP) targets proteins to the endoplasmic reticulum (ER). SRP recognizes the ribosome synthesizing a signal sequence and delivers it to the SRP receptor (SR) on the ER membrane followed by the transfer of the signal sequence to the translocon. Here, we present the cryo-electron microscopy structure of the mammalian translating ribosome in complex with SRP and SR in a conformation preceding signal sequence handover. The structure visualizes all eukaryotic-specific SRP and SR proteins and reveals their roles in stabilizing this conformation by forming a large protein assembly at the distal site of SRP RNA. We provide biochemical evidence that the guanosine triphosphate hydrolysis of SRP·SR is delayed at this stage, possibly to provide a time window for signal sequence handover to the translocon.

Publication types

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

MeSH terms

  • Animals
  • Cryoelectron Microscopy
  • GTP Phosphohydrolases / chemistry
  • Guanosine Triphosphate / chemistry
  • Hydrolysis
  • Protein Conformation
  • Protein Multimerization
  • Protein Sorting Signals*
  • RNA / chemistry
  • Receptors, Cytoplasmic and Nuclear / chemistry*
  • Receptors, Cytoplasmic and Nuclear / ultrastructure
  • Receptors, Peptide / chemistry*
  • Receptors, Peptide / ultrastructure
  • Ribosomes / chemistry*
  • Ribosomes / ultrastructure


  • Protein Sorting Signals
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Peptide
  • signal peptide receptor
  • RNA
  • Guanosine Triphosphate
  • GTP Phosphohydrolases