TY - JOUR
T1 - Homodimerization of the G protein SRβ in the nucleotide-free state involves proline cis/trans isomerization in the switch II region
AU - Schwartz, Thomas U.
AU - Schmidt, Daniel
AU - Brohawn, Stephen G.
AU - Blobel, Günter
PY - 2006/5/2
Y1 - 2006/5/2
N2 - 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.
AB - 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.
KW - Cotranslational transport
KW - Proline isomerization
KW - Signal-recognition particle receptor
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U2 - 10.1073/pnas.0602083103
DO - 10.1073/pnas.0602083103
M3 - Article
C2 - 16627619
AN - SCOPUS:33646530528
SN - 0027-8424
VL - 103
SP - 6823
EP - 6828
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 18
ER -