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

Proceedings of the National Academy of Sciences of the United States of America
Thomas U SchwartzGünter Blobel

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.

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Citations

May 2, 2013·Acta Crystallographica. Section D, Biological Crystallography·Kai En ChenJennifer Martin
Aug 12, 2009·Journal of Experimental & Clinical Cancer Research : CR·Yaqing ZhangWei Yan
Mar 15, 2013·The Journal of Biological Chemistry·Stephanie Hoffmann-ThomsFranz X Schmid
Aug 11, 2010·The Journal of Cell Biology·James R R Whittle, Thomas U Schwartz
Nov 3, 2016·Chemistry : a European Journal·Kamran T Mahmudov, Armando J L Pombeiro
Nov 7, 2008·Journal of Computational Chemistry·Young Kee Kang, Nam Sook Kang
Oct 12, 2007·The Journal of Physical Chemistry. B·Young Kee Kang, Hae Sook Park
Oct 19, 2010·The Journal of Physical Chemistry. B·Byung Jin ByunYoung Kee Kang
Oct 22, 2008·The International Journal of Biochemistry & Cell Biology·T Cavalier-Smith

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