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Molecular Crosstalk between the Nucleotide Specificity Determinant of the SRP GTPase and the SRP Receptor

Shan, Shu-ou and Walter, Peter (2005) Molecular Crosstalk between the Nucleotide Specificity Determinant of the SRP GTPase and the SRP Receptor. Biochemistry, 44 (16). pp. 6214-6222. ISSN 0006-2960. doi:10.1021/bi0500980. https://resolver.caltech.edu/CaltechAUTHORS:20170131-140941855

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Abstract

In signal recognition particle (SRP)-dependent targeting of proteins to the bacterial plasma membrane, two GTPases, Ffh (the SRP GTPase) and FtsY (the receptor GTPase), form a complex in which both proteins reciprocally stimulate each other's GTPase activities. We mutated Asp251 in the Ffh active site to Asn (D251N), converting Ffh to a xanthosine 5‘-triphosphate (XTP)-specific protein as has been observed in many other GTPases. Unexpectedly, mutant SRP(D251N) is severely compromised in the formation of an active SRP·FtsY complex when bound with cognate XTP, and even more surprisingly, mutant SRP(D251N) works better when bound with noncognate GTP. These paradoxical results are explained by a model in which Ffh Asp251 forms a bidentate interaction with not only the bound GTP but also the receptor FtsY across the dimer interface. These interactions form part of the network that seals the lateral entrance to the composite active site at the dimer interface, thereby ensuring the electrostatic and/or structural integrity of the active site and contributing to the formation of an active SRP·FtsY complex.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/bi0500980DOIArticle
http://pubs.acs.org/doi/abs/10.1021/bi0500980PublisherArticle
http://pubs.acs.org/doi/suppl/10.1021/bi0500980Related ItemSupporting Information
ORCID:
AuthorORCID
Shan, Shu-ou0000-0002-6526-1733
Additional Information:© 2005 American Chemical Society. Received 17 January 2005. Published online 5 April 2005. Published in print 1 April 2005. This work was supported by NIH Grant GM 32384 to P.W. P.W. is an Investigator of the Howard Hughes Medical Institute. S.S. was a Cancer Research Fund Fellow of the Damon Runyon-Walter Winchell Foundation when this work began and is now a Burroughs Wellcome Fund Fellow. We thank Dr. Henry Bourne, Daniel Herschlag, Geeta J. Narlikar, and members of the Walter lab for helpful comments on the manuscript.
Funders:
Funding AgencyGrant Number
NIHGM-32384
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Damon Runyon-Walter Winchell Cancer FundUNSPECIFIED
Burroughs Wellcome FundUNSPECIFIED
Issue or Number:16
DOI:10.1021/bi0500980
Record Number:CaltechAUTHORS:20170131-140941855
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170131-140941855
Official Citation:Molecular Crosstalk between the Nucleotide Specificity Determinant of the SRP GTPase and the SRP Receptor Shu-ou Shan and Peter Walter Biochemistry 2005 44 (16), 6214-6222 DOI: 10.1021/bi0500980
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:73893
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:01 Feb 2017 00:13
Last Modified:11 Nov 2021 05:23

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