title: Characterization of an Additional Binding Surface on the p97 N-Terminal Domain Involved in Bipartite Cofactor Interactions.
abstract: The type II AAA ATPase p97 interacts with a large number of cofactors that regulate its function by recruiting it to different cellular pathways. Most of the cofactors interact with the N-terminal (N) domain of p97, either via ubiquitin-like domains or short linear binding motifs. While some linear binding motifs form α helices, another group features short stretches of unstructured hydrophobic sequences as found in the so-called SHP (BS1, binding segment 1) motif. Here we present the crystal structure of a SHP-binding motif in complex with p97, which reveals a so far uncharacterized binding site on the p97 N domain that is different from the conserved binding surface of all other known p97 cofactors. This finding explains how cofactors like UFD1/NPL4 and p47 can utilize a bipartite binding mechanism to interact simultaneously with the same p97 monomer via their ubiquitin-like domain and SHP motif.
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: D033942:Adaptor Proteins, Vesicular Transport; D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D003067:Coenzymes / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D003067:Coenzymes; D047908:Intracellular Signaling Peptides and Proteins; C514112:NPLOC4 protein, human; D009687:Nuclear Proteins; D011506:Proteins; C491497:UFD1 protein, human; D000251:Adenosine Triphosphatases; C404942:p97 ATPase