PMID:12242434

Citation	Hunt, JF, Weinkauf, S, Henry, L, Fak, JJ, McNicholas, P, Oliver, DB and Deisenhofer, J (2002) Nucleotide control of interdomain interactions in the conformational reaction cycle of SecA. Science 297:2018-26
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.
Links	PubMed Online version:10.1126/science.1074424
Keywords	Adenosine Diphosphate/chemistry; Adenosine Diphosphate/metabolism; Adenosine Triphosphatases/chemistry; Adenosine Triphosphatases/metabolism; Adenosine Triphosphate/chemistry; Adenosine Triphosphate/metabolism; Amino Acid Motifs; Amino Acid Sequence; Bacillus subtilis/enzymology; Bacterial Proteins/chemistry; Bacterial Proteins/metabolism; Binding Sites; Crystallization; Crystallography, X-Ray; DNA Helicases/chemistry; DNA, Bacterial/chemistry; DNA, Bacterial/metabolism; DNA, Single-Stranded/chemistry; DNA, Single-Stranded/metabolism; Dimerization; Escherichia coli; Escherichia coli Proteins/chemistry; Escherichia coli Proteins/metabolism; Eukaryotic Initiation Factor-4A; Fluorescence Polarization; Fourier Analysis; Hydrogen Bonding; Ligands; Membrane Transport Proteins/chemistry; Membrane Transport Proteins/metabolism; Models, Molecular; Molecular Sequence Data; Peptide Initiation Factors/chemistry; Peptides/chemistry; Protein Binding; Protein Conformation; Protein Folding; Protein Precursors/metabolism; Protein Structure, Secondary; Protein Structure, Tertiary; Temperature
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