The General Definition of the p97/Valosin-containing Protein (VCP)-interacting Motif (VIM) Delineates a New Family of p97 Cofactors
| Autor: | Christopher Stapf, Edward J. P. Cartwright, Mark Bycroft, Alexander Buchberger, Kay Hofmann |
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| Rok vydání: | 2011 |
| Předmět: |
Magnetic Resonance Spectroscopy
Valosin-containing protein Amino Acid Motifs Molecular Sequence Data Autophagy-Related Proteins Cell Cycle Proteins Computational biology Protein degradation Biochemistry Ubiquitin Valosin Containing Protein Two-Hybrid System Techniques polycyclic compounds Consensus sequence Humans Amino Acid Sequence Binding site Molecular Biology Peptide sequence Ultrabithorax Adaptor Proteins Signal Transducing Adenosine Triphosphatases Binding Sites Sequence Homology Amino Acid biology Computational Biology Cell Biology biochemical phenomena metabolism and nutrition bacterial infections and mycoses AAA proteins Protein Structure Tertiary Adaptor Proteins Vesicular Transport HEK293 Cells Protein Structure and Folding biology.protein Carrier Proteins |
| Zdroj: | Journal of Biological Chemistry. 286:38670-38678 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m111.274472 |
| Popis: | Cellular functions of the essential, ubiquitin-selective AAA ATPase p97/valosin-containing protein (VCP) are controlled by regulatory cofactors determining substrate specificity and fate. Most cofactors bind p97 through a ubiquitin regulatory X (UBX) or 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 RX(5)AAX(2)R as a general definition of the VIM that unites a novel family of known and putative p97 cofactors, 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 N-terminal domain (N domain) that are critical for VIM binding. Importantly, we show that cellular stress resistance conferred by the yeast VIM-containing cofactor 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 cofactors. |
| Databáze: | OpenAIRE |
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