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Induced nucleotide specificity in a GTPase

Shan, Shu-ou and Walter, Peter (2003) Induced nucleotide specificity in a GTPase. Proceedings of the National Academy of Sciences of the United States of America, 100 (8). pp. 4480-4485. ISSN 0027-8424. PMCID PMC153581. doi:10.1073/pnas.0737693100. https://resolver.caltech.edu/CaltechAUTHORS:20190918-102339005

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Abstract

In signal-recognition particle (SRP)-dependent protein targeting to the bacterial plasma membrane, two GTPases, Ffh (a subunit of the bacterial SRP) and FtsY (the bacterial SRP receptor), act as GTPase activating proteins for one another. The molecular mechanism of this reciprocal GTPase activation is poorly understood. In this work, we show that, unlike other GTPases, free FtsY exhibits only low preference for GTP over other nucleotides. On formation of the SRP⋅FtsY complex, however, the nucleotide specificity of FtsY is enhanced 10^3-fold. Thus, interactions with SRP must induce conformational changes that directly affect the FtsY GTP-binding site: in response to SRP binding, FtsY switches from a nonspecific “open” state to a “closed” state that provides discrimination between cognate and noncognate nucleotides. We propose that this conformational change leads to more accurate positioning of the nucleotide and thus could contribute to activation of FtsY's GTPase activity by a novel mechanism.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1073/pnas.0737693100DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC153581PubMed CentralArticle
ORCID:
AuthorORCID
Shan, Shu-ou0000-0002-6526-1733
Additional Information:© 2003 The National Academy of Sciences. Edited by Jennifer A. Doudna, University of California, Berkeley, CA, and approved February 5, 2003 (received for review December 17, 2002). We thank A. E. Johnson for advice on fluorescence experiments and T. Powers, R. Gilmore, H. Bourne, R. Stroud, and members of the Walter and Stroud laboratories for comments on the manuscript. This work was supported by National Institutes of Health Grant GM 32384 (to P.W.). P.W. is an Investigator of the Howard Hughes Medical Institute, and S.S. is a Cancer Research Fund Fellow of the Damon Runyon–Walter Winchell Foundation. This paper was submitted directly (Track II) to the PNAS office.
Funders:
Funding AgencyGrant Number
NIHGM 32384
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Damon Runyon-Walter Winchell FoundationUNSPECIFIED
Issue or Number:8
PubMed Central ID:PMC153581
DOI:10.1073/pnas.0737693100
Record Number:CaltechAUTHORS:20190918-102339005
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190918-102339005
Official Citation:Induced nucleotide specificity in a GTPase. Shu-ou Shan, Peter Walter. Proceedings of the National Academy of Sciences Apr 2003, 100 (8) 4480-4485; DOI: 10.1073/pnas.0737693100
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:98717
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:18 Sep 2019 18:03
Last Modified:16 Nov 2021 17:41

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