Functional changes in the structure of the SRP GTPase on binding GDP and Mg2+GDP

Douglas M. Freymann; Robert J. Keenan; Robert M. Stroud; Peter Walter

doi:10.1038/11572

Functional changes in the structure of the SRP GTPase on binding GDP and Mg²⁺GDP

Douglas M. Freymann^*, Robert J. Keenan, Robert M. Stroud, Peter Walter

^*Corresponding author for this work

Pharmacology

Research output: Contribution to journal › Article › peer-review

74 Scopus citations

Abstract

Ffh is a component of a bacterial ribonucleoprotein complex homologous to the signal recognition particle (SRP) of eukaryotes. It comprises three domains that mediate both binding to the hydrophobic signal sequence of the nascent polypeptide and the GTP-dependent interaction of Ffh with a structurally homologous GTPase of the SRP receptor. The X-ray structures of the two-domain 'NG' GTPase of Ffh in complex with Mg²⁺GDP and GDP have been determined at 2.0 Å resolution. The structures explain the low nucleotide affinity of Ffh and locate two regions of structural mobility at opposite sides of the nucleotide-binding site. One of these regions includes highly conserved sequence motifs that presumably contribute to the structural trigger signaling the GTP-bound state. The other includes the highly conserved interface between the N and G domains, and supports the hypothesis that the N domain regulates or signals the nucleotide occupancy of the G domain.

Original language	English (US)
Pages (from-to)	793-801
Number of pages	9
Journal	Nature Structural Biology
Volume	6
Issue number	8
DOIs	https://doi.org/10.1038/11572
State	Published - 1999

Funding

We thank J. Richardson of Duke University for an illuminating discussion. This work was begun while D.M.F. was a postdoctoral fellow in the laboratories of P.W. and R.M.S. It was supported by grants to P.W. and R.M.S. from the NIH and by the Herb Boyer Fund and the Biotechnology Program of the University of California. It is based in part on research conducted at the Stanford Synchrotron Radiation Laboratory (SSRL), a facility funded by the Department of Energy, Office of Basic Energy Sciences. P.W. is an investigator in the Howard Hughes Medical Institute.

ASJC Scopus subject areas

Structural Biology
Biochemistry
Genetics

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10.1038/11572

Cite this

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title = "Functional changes in the structure of the SRP GTPase on binding GDP and Mg2+GDP",

abstract = "Ffh is a component of a bacterial ribonucleoprotein complex homologous to the signal recognition particle (SRP) of eukaryotes. It comprises three domains that mediate both binding to the hydrophobic signal sequence of the nascent polypeptide and the GTP-dependent interaction of Ffh with a structurally homologous GTPase of the SRP receptor. The X-ray structures of the two-domain 'NG' GTPase of Ffh in complex with Mg2+GDP and GDP have been determined at 2.0 {\AA} resolution. The structures explain the low nucleotide affinity of Ffh and locate two regions of structural mobility at opposite sides of the nucleotide-binding site. One of these regions includes highly conserved sequence motifs that presumably contribute to the structural trigger signaling the GTP-bound state. The other includes the highly conserved interface between the N and G domains, and supports the hypothesis that the N domain regulates or signals the nucleotide occupancy of the G domain.",

author = "Freymann, {Douglas M.} and Keenan, {Robert J.} and Stroud, {Robert M.} and Peter Walter",

note = "Funding Information: We thank J. Richardson of Duke University for an illuminating discussion. This work was begun while D.M.F. was a postdoctoral fellow in the laboratories of P.W. and R.M.S. It was supported by grants to P.W. and R.M.S. from the NIH and by the Herb Boyer Fund and the Biotechnology Program of the University of California. It is based in part on research conducted at the Stanford Synchrotron Radiation Laboratory (SSRL), a facility funded by the Department of Energy, Office of Basic Energy Sciences. P.W. is an investigator in the Howard Hughes Medical Institute.",

year = "1999",

doi = "10.1038/11572",

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journal = "Nature Structural Biology",

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AU - Freymann, Douglas M.

AU - Keenan, Robert J.

AU - Stroud, Robert M.

AU - Walter, Peter

N1 - Funding Information: We thank J. Richardson of Duke University for an illuminating discussion. This work was begun while D.M.F. was a postdoctoral fellow in the laboratories of P.W. and R.M.S. It was supported by grants to P.W. and R.M.S. from the NIH and by the Herb Boyer Fund and the Biotechnology Program of the University of California. It is based in part on research conducted at the Stanford Synchrotron Radiation Laboratory (SSRL), a facility funded by the Department of Energy, Office of Basic Energy Sciences. P.W. is an investigator in the Howard Hughes Medical Institute.

PY - 1999

Y1 - 1999

N2 - Ffh is a component of a bacterial ribonucleoprotein complex homologous to the signal recognition particle (SRP) of eukaryotes. It comprises three domains that mediate both binding to the hydrophobic signal sequence of the nascent polypeptide and the GTP-dependent interaction of Ffh with a structurally homologous GTPase of the SRP receptor. The X-ray structures of the two-domain 'NG' GTPase of Ffh in complex with Mg2+GDP and GDP have been determined at 2.0 Å resolution. The structures explain the low nucleotide affinity of Ffh and locate two regions of structural mobility at opposite sides of the nucleotide-binding site. One of these regions includes highly conserved sequence motifs that presumably contribute to the structural trigger signaling the GTP-bound state. The other includes the highly conserved interface between the N and G domains, and supports the hypothesis that the N domain regulates or signals the nucleotide occupancy of the G domain.

AB - Ffh is a component of a bacterial ribonucleoprotein complex homologous to the signal recognition particle (SRP) of eukaryotes. It comprises three domains that mediate both binding to the hydrophobic signal sequence of the nascent polypeptide and the GTP-dependent interaction of Ffh with a structurally homologous GTPase of the SRP receptor. The X-ray structures of the two-domain 'NG' GTPase of Ffh in complex with Mg2+GDP and GDP have been determined at 2.0 Å resolution. The structures explain the low nucleotide affinity of Ffh and locate two regions of structural mobility at opposite sides of the nucleotide-binding site. One of these regions includes highly conserved sequence motifs that presumably contribute to the structural trigger signaling the GTP-bound state. The other includes the highly conserved interface between the N and G domains, and supports the hypothesis that the N domain regulates or signals the nucleotide occupancy of the G domain.

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Functional changes in the structure of the SRP GTPase on binding GDP and Mg²⁺GDP

Abstract

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N AND GTPASE DOMAINS OF THE SIGNAL SEQUENCE RECOGNITION PROTEIN FFH FROM THERMUS AQUATICUS

N AND GTPASE DOMAINS OF THE SIGNAL SEQUENCE RECOGNITION PROTEIN FFH FROM THERMUS AQUATICUS

N AND GTPASE DOMAINS OF THE SIGNAL SEQUENCE RECOGNITION PROTEIN FFH FROM THERMUS AQUATICUS

Cite this

Functional changes in the structure of the SRP GTPase on binding GDP and Mg2+GDP

Abstract

Funding

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Datasets

N AND GTPASE DOMAINS OF THE SIGNAL SEQUENCE RECOGNITION PROTEIN FFH FROM THERMUS AQUATICUS

N AND GTPASE DOMAINS OF THE SIGNAL SEQUENCE RECOGNITION PROTEIN FFH FROM THERMUS AQUATICUS

N AND GTPASE DOMAINS OF THE SIGNAL SEQUENCE RECOGNITION PROTEIN FFH FROM THERMUS AQUATICUS

Cite this

Functional changes in the structure of the SRP GTPase on binding GDP and Mg²⁺GDP