ATP-bound form of the D1 AAA domain inhibits an essential function of Cdc48p/p97This paper is one of a selection of papers published in this special issue entitled 8th International Conference on AAA Proteins and has undergone the Journal's usual peer review process.

DOI Web Site Web Site 11 Citations 45 References
  • Masatoshi Esaki
    Department of Molecular Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
  • Teru Ogura
    Department of Molecular Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.

Description

<jats:p>Cdc48p/p97 is a highly conserved essential AAA protein that is required for many cellular processes, and is identified as a causative gene for an autosomal dominant human disorder, inclusion body myopathy associated with Paget’s disease of the bone and frontotemporal dementia (IBMPFD). Cdc48p/p97 is composed of an N-terminal domain, followed by two AAA domains (D1 and D2) whose ATPase activities have been characterized extensively. In this study, effects of mutations on the essential functions of yeast Cdc48p/p97 in vivo were systematically analyzed. IBMPFD-related mutations do not affect the essential functions of Cdc48p/p97. Loss of ATPase activity of D2 leads to loss of function of the protein in vivo. In contrast, ATPase activity of D1 per se is not essential, but a mutation locking D1 in an ATP-bound form is exceptionally lethal. Site-directed and random mutagenesis analyses suggest that the ATP-bound form of D1 changes an inter-domain interaction, thereby perturbing an essential function of Cdc48p/p97.</jats:p>

Journal

Citations (11)*help

See more

References(45)*help

See more

Related Projects

See more

Keywords

Report a problem

Back to top