title: Homodimerization of the G protein SRbeta in the nucleotide-free state involves proline cis/trans isomerization in the switch II region.
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 alpha- and beta-subunits of SR. We have determined the 2.2-A crystal structure of the nucleotide-free SRbeta 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 SRalpha binding. The switch mechanism involves cis/trans isomerization of a strictly conserved proline, potentially implying a new layer of regulation of cotranslational transport.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. tus@mit.edu
authors.forename: Thomas U
authors.initials: TU
authors.lastname: Schwartz
authors.forename: Daniel
authors.initials: D
authors.lastname: Schmidt
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Brohawn
authors.forename: Günter
authors.initials: G
authors.lastname: Blobel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D007536:Isomerism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011392:Proline / Q000737:chemistry*; D020836:Protein Structure, Quaternary; D021122:Protein Subunits / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018000:Receptors, Peptide / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D021122:Protein Subunits; D018160:Receptors, Cytoplasmic and Nuclear; D018000:Receptors, Peptide; C036318:signal peptide receptor; D011392:Proline