Homodimerization of the G protein SRβ in the nucleotide-free state involves proline cis/trans isomerization in the switch II region

Thomas U. Schwartz, Daniel Schmidt, Stephen G. Brohawn, Günter Blobel

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Protein translocation across and insertion into membranes is essential to all life forms. Signal peptide-bearing nascent polypeptide chains emerging from the ribosome are first sampled by the signal-recognition particle (SRP), then targeted to the membrane via the SRP receptor (SR), and, finally, transferred to the protein-conducting channel. In eukaryotes, this process is tightly controlled by the concerted action of three G proteins, the 54-kD subunit of SRP and the α- and β-subunits of SR. We have determined the 2.2-Å crystal structure of the nucleotide-free SRβ domain. Unexpectedly, the structure is a homodimer with a highly intertwined interface made up of residues from the switch regions of the G domain. The remodeling of the switch regions does not resemble any of the known G protein switch mechanisms. Biochemical analysis confirms homodimerization in vitro, which is incompatible with SRα binding. The switch mechanism involves cis/trans isomerization of a strictly conserved proline, potentially implying a new layer of regulation of cotranslational transport.

Original languageEnglish (US)
Pages (from-to)6823-6828
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number18
DOIs
StatePublished - May 2 2006

Keywords

  • Cotranslational transport
  • Proline isomerization
  • Signal-recognition particle receptor

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