Structural and mechanistic insights into the arginine/lysine-rich peptide motifs that interact with P97/VCP.

P97 protein, also referred to as valosin-containing protein (VCP), is an AAA-ATPase (ATPase associated with a variety of cellular activities) that mediates vital cellular activities with the cooperation of many cofactors. A group of cofactors interact with the N-terminal domain of P97 (P97N) through their Arg/Lys-rich peptide motifs. We investigated ...
the interactions between P97 and these motifs, including VCP-binding motif (VBM) and VCP-interacting motif (VIM). The solution structures of the VBM motif from HRD1 and the VIM motif from SVIP are both comprised mainly of a single α-helix. The VIM motifs generally have stronger P97N-binding affinities than the VBMs, and SVIP (VIM) can compete with HRD1-VBM for the interaction, providing a possibility that VIM-containing proteins (such as SVIP) act as competitors against VBM-containing proteins (such as HRD1) for interacting with P97. Based on biochemical features of the VBM motifs, we also identified NUB1L (NEDD8 ultimate buster-1 long) as a novel VBM-containing protein, which is involved in proteasomal degradation of NEDD8 through the P97 pathway.
Mesh Terms:
Adenosine Triphosphatases, Amino Acid Motifs, Arginine, Carrier Proteins, Cell Cycle Proteins, HEK293 Cells, Humans, Membrane Proteins, Peptides, Proline, Proteasome Endopeptidase Complex, Protein Binding, Proteolysis, Transcription Factors, Ubiquitin-Protein Ligases, Ubiquitins
Biochim. Biophys. Acta
Date: Dec. 01, 2013
Download Curated Data For This Publication
163443
Switch View:
  • Interactions 11