title: Structural Basis of ATP Hydrolysis and Intersubunit Signaling in the AAA+ ATPase p97.
abstract: p97 belongs to the superfamily of AAA+ ATPases and is characterized by a tandem AAA module, an N-terminal domain involved in substrate and cofactor interactions, and a functionally important unstructured C-terminal tail. The ATPase activity is controlled by an intradomain communication within the same protomer and an interdomain communication between neighboring protomers. Here, we present for the first time crystal structures in which the physiologically relevant p97 hexamer constitutes the content of the asymmetric unit, namely in the apo state without nucleotide in either the D1 or D2 module and in the pre-activated state with ATPγS bound to both modules. The structures provide new mechanistic insights into the interdomain communication mediated by conformational changes of the C terminus as well as an intersubunit signaling network, which couples the nucleotide state to the conformation of the central putative substrate binding pore.
authors.affiliation: Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Josef-Schneider-Strasse 2, 97080 Würzburg, Germany. Electronic address: petra.haenzelmann@virchow.uni-wuerzburg.de.
authors.forename: Petra
authors.initials: P
authors.lastname: Hänzelmann
authors.affiliation: Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Josef-Schneider-Strasse 2, 97080 Würzburg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Schindelin
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites; D006801:Humans; D006868:Hydrolysis; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D009687:Nuclear Proteins; D021122:Protein Subunits; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; C404942:p97 ATPase