Nucleotide control of interdomain interactions in the conformational reaction cycle of SecA

John F. Hunt, Sevil Weinkauf, Lisa Henry, John J. Fak, Paul McNicholas, Donald B. Oliver, Johann Deisenhofer

Research output: Contribution to journalArticle

225 Citations (Scopus)

Abstract

The SecA adenosine triphosphatase (ATPase) mediates extrusion of the amino termini of secreted proteins from the eubacterial cytosol based on cycles of reversible binding to the SecYEG translocon. We have determined the crystal structure of SecA with and without magnesium-adenosine diphosphate bound to the high-affinity ATPase site at 3.0 and 2.7 angstrom resolution, respectively. Candidate sites for preprotein binding are located on a surface containing the SecA epitopes exposed to the periplasm upon binding to SecYEG and are thus positioned to deliver preprotein to SecYEG. Comparisons with structurally related ATPases, including superfamily I and II ATP-dependent helicases, suggest that the interaction geometry of the tandem motor domains in SecA is modulated by nucleotide binding, which is shown by fluorescence anisotropy experiments to reverse an endothermic domain-dissociation reaction hypothesized to gate binding to SecYEG.

Original languageEnglish (US)
Pages (from-to)2018-2026
Number of pages9
JournalScience
Volume297
Issue number5589
DOIs
StatePublished - Sep 20 2002

Fingerprint

Adenosine Triphosphatases
Nucleotides
Periplasm
Fluorescence Polarization
Cytosol
Adenosine Diphosphate
Magnesium
Epitopes
Adenosine Triphosphate
Binding Sites
Proteins

ASJC Scopus subject areas

  • General

Cite this

Hunt, J. F., Weinkauf, S., Henry, L., Fak, J. J., McNicholas, P., Oliver, D. B., & Deisenhofer, J. (2002). Nucleotide control of interdomain interactions in the conformational reaction cycle of SecA. Science, 297(5589), 2018-2026. https://doi.org/10.1126/science.1074424

Nucleotide control of interdomain interactions in the conformational reaction cycle of SecA. / Hunt, John F.; Weinkauf, Sevil; Henry, Lisa; Fak, John J.; McNicholas, Paul; Oliver, Donald B.; Deisenhofer, Johann.

In: Science, Vol. 297, No. 5589, 20.09.2002, p. 2018-2026.

Research output: Contribution to journalArticle

Hunt, JF, Weinkauf, S, Henry, L, Fak, JJ, McNicholas, P, Oliver, DB & Deisenhofer, J 2002, 'Nucleotide control of interdomain interactions in the conformational reaction cycle of SecA', Science, vol. 297, no. 5589, pp. 2018-2026. https://doi.org/10.1126/science.1074424
Hunt JF, Weinkauf S, Henry L, Fak JJ, McNicholas P, Oliver DB et al. Nucleotide control of interdomain interactions in the conformational reaction cycle of SecA. Science. 2002 Sep 20;297(5589):2018-2026. https://doi.org/10.1126/science.1074424
Hunt, John F. ; Weinkauf, Sevil ; Henry, Lisa ; Fak, John J. ; McNicholas, Paul ; Oliver, Donald B. ; Deisenhofer, Johann. / Nucleotide control of interdomain interactions in the conformational reaction cycle of SecA. In: Science. 2002 ; Vol. 297, No. 5589. pp. 2018-2026.
@article{d83648b92084424ab6e7fd7d94113432,
title = "Nucleotide control of interdomain interactions in the conformational reaction cycle of SecA",
abstract = "The SecA adenosine triphosphatase (ATPase) mediates extrusion of the amino termini of secreted proteins from the eubacterial cytosol based on cycles of reversible binding to the SecYEG translocon. We have determined the crystal structure of SecA with and without magnesium-adenosine diphosphate bound to the high-affinity ATPase site at 3.0 and 2.7 angstrom resolution, respectively. Candidate sites for preprotein binding are located on a surface containing the SecA epitopes exposed to the periplasm upon binding to SecYEG and are thus positioned to deliver preprotein to SecYEG. Comparisons with structurally related ATPases, including superfamily I and II ATP-dependent helicases, suggest that the interaction geometry of the tandem motor domains in SecA is modulated by nucleotide binding, which is shown by fluorescence anisotropy experiments to reverse an endothermic domain-dissociation reaction hypothesized to gate binding to SecYEG.",
author = "Hunt, {John F.} and Sevil Weinkauf and Lisa Henry and Fak, {John J.} and Paul McNicholas and Oliver, {Donald B.} and Johann Deisenhofer",
year = "2002",
month = "9",
day = "20",
doi = "10.1126/science.1074424",
language = "English (US)",
volume = "297",
pages = "2018--2026",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "5589",

}

TY - JOUR

T1 - Nucleotide control of interdomain interactions in the conformational reaction cycle of SecA

AU - Hunt, John F.

AU - Weinkauf, Sevil

AU - Henry, Lisa

AU - Fak, John J.

AU - McNicholas, Paul

AU - Oliver, Donald B.

AU - Deisenhofer, Johann

PY - 2002/9/20

Y1 - 2002/9/20

N2 - The SecA adenosine triphosphatase (ATPase) mediates extrusion of the amino termini of secreted proteins from the eubacterial cytosol based on cycles of reversible binding to the SecYEG translocon. We have determined the crystal structure of SecA with and without magnesium-adenosine diphosphate bound to the high-affinity ATPase site at 3.0 and 2.7 angstrom resolution, respectively. Candidate sites for preprotein binding are located on a surface containing the SecA epitopes exposed to the periplasm upon binding to SecYEG and are thus positioned to deliver preprotein to SecYEG. Comparisons with structurally related ATPases, including superfamily I and II ATP-dependent helicases, suggest that the interaction geometry of the tandem motor domains in SecA is modulated by nucleotide binding, which is shown by fluorescence anisotropy experiments to reverse an endothermic domain-dissociation reaction hypothesized to gate binding to SecYEG.

AB - The SecA adenosine triphosphatase (ATPase) mediates extrusion of the amino termini of secreted proteins from the eubacterial cytosol based on cycles of reversible binding to the SecYEG translocon. We have determined the crystal structure of SecA with and without magnesium-adenosine diphosphate bound to the high-affinity ATPase site at 3.0 and 2.7 angstrom resolution, respectively. Candidate sites for preprotein binding are located on a surface containing the SecA epitopes exposed to the periplasm upon binding to SecYEG and are thus positioned to deliver preprotein to SecYEG. Comparisons with structurally related ATPases, including superfamily I and II ATP-dependent helicases, suggest that the interaction geometry of the tandem motor domains in SecA is modulated by nucleotide binding, which is shown by fluorescence anisotropy experiments to reverse an endothermic domain-dissociation reaction hypothesized to gate binding to SecYEG.

UR - http://www.scopus.com/inward/record.url?scp=0037144467&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037144467&partnerID=8YFLogxK

U2 - 10.1126/science.1074424

DO - 10.1126/science.1074424

M3 - Article

C2 - 12242434

AN - SCOPUS:0037144467

VL - 297

SP - 2018

EP - 2026

JO - Science

JF - Science

SN - 0036-8075

IS - 5589

ER -