Mechanism of association and reciprocal activation of two GTPases

PLoS Biology
Shu-ou ShanPeter Walter

Abstract

The signal recognition particle (SRP) mediates the cotranslational targeting of nascent proteins to the eukaryotic endoplasmic reticulum membrane or the bacterial plasma membrane. During this process, two GTPases, one in SRP and one in the SRP receptor (named Ffh and FtsY in bacteria, respectively), form a complex in which both proteins reciprocally activate the GTPase reaction of one another. Here, we explore by site-directed mutagenesis the role of 45 conserved surface residues in the Ffh-FtsY interaction. Mutations of a large number of residues at the interface impair complex formation, supporting the importance of an extensive interaction surface. Surprisingly, even after a stable complex is formed, single mutations in FtsY can block the activation of GTP hydrolysis in both active sites. Thus, activation requires conformational changes across the interface that coordinate the positioning of catalytic residues in both GTPase sites. A distinct class of mutants exhibits half-site reactivity and thus allows us to further uncouple the activation of individual GTPases. Our dissection of the activation process suggests discrete conformational stages during formation of the active SRP*SRP receptor complex. Each stage provides a pot...Continue Reading

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Citations

Aug 19, 2007·Proceedings of the National Academy of Sciences of the United States of America·Gert BangeIrmgard Sinning
Feb 19, 2013·Annual Review of Biochemistry·David AkopianShu-ou Shan
Jun 5, 2014·Annual Review of Biophysics·Xin Zhang, Shu-ou Shan
Jun 11, 2014·The Journal of Cell Biology·Ishu SaraogiShu-Ou Shan
Apr 14, 2010·Proceedings of the National Academy of Sciences of the United States of America·Kuang Shen, Shu-ou Shan
Nov 4, 2006·Nature Structural & Molecular Biology·Kakoli MitraArnold Driessen
Mar 10, 2007·Microbiology and Molecular Biology Reviews : MMBR·Hay-Oak Park, Erfei Bi
Sep 23, 2008·Journal of Bacteriology·James M Peterson, Gregory J Phillips
Jan 28, 2009·Nature Structural & Molecular Biology·Saskia B NeherPeter Walter
Apr 6, 2011·Proceedings of the National Academy of Sciences of the United States of America·Xin ZhangShu-ou Shan
Jan 10, 2012·The Journal of Biological Chemistry·Dawei Zhang, Shu-ou Shan
Jun 16, 2012·Genetics·Erfei Bi, Hay-Oak Park
Aug 12, 2005·Molecular Membrane Biology·Martin R Pool
Feb 13, 2013·The Journal of Cell Biology·David AkopianShu-ou Shan
Aug 23, 2006·The Journal of Cell Biology·Sandra AngeliniHans-Georg Koch
Dec 23, 2006·Journal of Structural Biology·Joseph Gawronski-Salerno, Douglas M Freymann
Sep 8, 2011·Protein Science : a Publication of the Protein Society·Ishu SaraogiShu-Ou Shan
Oct 16, 2015·The Journal of Cell Biology·Patrick KuhnHans-Georg Koch
Jan 29, 2009·Proceedings of the National Academy of Sciences of the United States of America·Xin ZhangShu-ou Shan
Dec 17, 2005·Trends in Biochemical Sciences·Alfred Wittinghofer
Feb 12, 2014·Biochimica Et Biophysica Acta·Ishu Saraogi, Shu-ou Shan
Nov 22, 2007·Current Biology : CB·Gert BangeIrmgard Sinning
Feb 1, 2005·FEBS Letters·Shu-ou Shan, Peter Walter
Dec 25, 2012·Journal of Bacteriology·Maren SchniederberendBarbara I Kazmierczak

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Methods Mentioned

BETA
GTPases
GTPase
nucleotide exchange
dissection
and
these
Fluorescence

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