Characterization of an Additional Binding Surface on the p97 N-Terminal Domain Involved in Bipartite Cofactor Interactions

Structure. 2016 Jan 5;24(1):140-147. doi: 10.1016/j.str.2015.10.027. Epub 2015 Dec 17.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport
  • Adenosine Triphosphatases / chemistry*
  • Adenosine Triphosphatases / metabolism
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Binding Sites
  • Coenzymes / chemistry
  • Coenzymes / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Molecular Sequence Data
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / metabolism
  • Protein Binding
  • Proteins / chemistry*
  • Proteins / metabolism


  • Adaptor Proteins, Vesicular Transport
  • Coenzymes
  • Intracellular Signaling Peptides and Proteins
  • NPLOC4 protein, human
  • Nuclear Proteins
  • Proteins
  • UFD1 protein, human
  • Adenosine Triphosphatases
  • p97 ATPase