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 journalArticlepeer-review

242 Scopus citations


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
Issue number5589
StatePublished - Sep 20 2002

ASJC Scopus subject areas

  • General


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