Ribosome-bound Get4/5 facilitates the capture of tail-anchored proteins by Sgt2 in yeast

Nat Commun. 2021 Feb 4;12(1):782. doi: 10.1038/s41467-021-20981-3.


The guided entry of tail-anchored proteins (GET) pathway assists in the posttranslational delivery of tail-anchored proteins, containing a single C-terminal transmembrane domain, to the ER. Here we uncover how the yeast GET pathway component Get4/5 facilitates capture of tail-anchored proteins by Sgt2, which interacts with tail-anchors and hands them over to the targeting component Get3. Get4/5 binds directly and with high affinity to ribosomes, positions Sgt2 close to the ribosomal tunnel exit, and facilitates the capture of tail-anchored proteins by Sgt2. The contact sites of Get4/5 on the ribosome overlap with those of SRP, the factor mediating cotranslational ER-targeting. Exposure of internal transmembrane domains at the tunnel exit induces high-affinity ribosome binding of SRP, which in turn prevents ribosome binding of Get4/5. In this way, the position of a transmembrane domain within nascent ER-targeted proteins mediates partitioning into either the GET or SRP pathway directly at the ribosomal tunnel exit.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Carrier Proteins / metabolism*
  • Cell Membrane / metabolism
  • Endoplasmic Reticulum / metabolism
  • Guanine Nucleotide Exchange Factors / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / isolation & purification
  • Membrane Proteins / metabolism*
  • Mutation
  • Peptide Chain Termination, Translational
  • Protein Binding
  • Protein Multimerization
  • Recombinant Proteins / genetics
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Ribosomal Proteins / metabolism
  • Ribosomes / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / isolation & purification
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Signal Recognition Particle / metabolism
  • Ubiquitin / genetics
  • Ubiquitin / isolation & purification
  • Ubiquitin / metabolism*


  • Carrier Proteins
  • GET4 protein, S cerevisiae
  • Guanine Nucleotide Exchange Factors
  • Mdy2 protein, S cerevisiae
  • Membrane Proteins
  • Recombinant Proteins
  • Ribosomal Proteins
  • Saccharomyces cerevisiae Proteins
  • Sgt2 protein, S cerevisiae
  • Signal Recognition Particle
  • Ubiquitin
  • Adenosine Triphosphatases
  • Get3 protein, S cerevisiae