Stapf C, Cartwright E, Bycroft M, Hofmann K, Buchberger A

Cellular functions of the essential, ubiquitin-selective AAA ATPase p97/Valosin-containing protein (VCP) are controlled by regulatory co-factors determining substrate specificity and fate. Most co-factors bind p97 through a UBX(-like) domain or linear sequence motifs, including the hitherto ill-defined p97/VCP-interacting motif (VIM). Here, we present the new, minimal consensus sequence R-x5-A-A-x2-R as ...

Read More

a general definition of the VIM that unites a novel family of known and putative p97 co-factors, among them UBXD1 and ZNF744/ANKZF1. We demonstrate that this minimal VIM consensus sequence is necessary and sufficient for p97 binding. Using NMR chemical shift mapping, we identified several residues of the p97 amino-terminal N domain that are critical for VIM binding. Importantly, we show that cellular stress resistance conferred by the yeast VIM-containing co-factor Vms1 depends on the physical interaction between its VIM and the critical N domain residues of the yeast p97 homolog, Cdc48. Thus, the VIM-N domain interaction characterized in this study is required for the physiological function of Vms1 and most likely other members of the newly defined VIM family of co-factors.

Date: Sep. 06, 2011

View in: Pubmed Google Scholar

124179