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

Authors:
Dr. Shuai Liu, PHD&MD;
Dr. Shuai Liu, PHD&MD;
Shandong Provincial hospital afflicated to Shandong University
Doctor, Surgeon
Urology
Jinan, Shandong | China
Qing-Shan Fu
Qing-Shan Fu
Institute of Biochemistry and Cell Biology
China
Jian Zhao
Jian Zhao
National Key Laboratory of Crop Genetic Improvement
China
Hong-Yu Hu
Hong-Yu Hu
Shanghai Institutes for Biological Sciences
China

Biochim Biophys Acta 2013 Dec 4;1834(12):2672-8. Epub 2013 Oct 4.

State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

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.

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Source
http://dx.doi.org/10.1016/j.bbapap.2013.09.021DOI Listing
December 2013
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