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Structure, dynamics and interactions of p47, a major adaptor of the AAA ATPase, p97
Author(s) -
Yuan Xuemei,
Simpson Peter,
Mckeown Ciaran,
Kondo Hisao,
Uchiyama Keiji,
Wallis Russell,
Dreveny Ingrid,
Keetch Catherine,
Zhang Xiaodong,
Robinson Carol,
Freemont Paul,
Matthews Stephen
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600152
Subject(s) - biology , aaa proteins , signal transducing adaptor protein , atpase , computational biology , dynamics (music) , microbiology and biotechnology , biochemistry , phosphorylation , enzyme , physics , acoustics
p47 is a major adaptor molecule of the cytosolic AAA ATPase p97. The principal role of the p97–p47 complex is in regulation of membrane fusion events. Mono‐ubiquitin recognition by p47 has also been shown to be crucial in the p97–p47‐mediated Golgi membrane fusion events. Here, we describe the high‐resolution solution structures of the N‐terminal UBA domain and the central domain (SEP) from p47. The p47 UBA domain has the characteristic three‐helix bundle fold and forms a highly stable complex with ubiquitin. We report the interaction surfaces of the two proteins and present a structure for the p47 UBA–ubiquitin complex. The p47 SEP domain adopts a novel fold with a βββααβ secondary structure arrangement, where β4 pairs in a parallel fashion to β1. Based on biophysical studies, we demonstrate a clear propensity for the self‐association of p47. Furthermore, p97 N binding abolishes p47 self‐association, revealing the potential interaction surfaces for recognition of other domains within p97 or the substrate.