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Nucleotide‐dependent conformational changes of the AAA+ ATPase p97 revisited
Author(s) -
Schuller Jan M.,
Beck Florian,
Lössl Philip,
Heck Albert J. R.,
Förster Friedrich
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12091
Subject(s) - aaa proteins , nucleotide , atpase , biophysics , chemistry , cryo electron microscopy , protein structure , conformational change , crystallography , biochemistry , biology , stereochemistry , enzyme , gene
The ubiquitous AAA‐ATPase p97 segregates ubiquitylated proteins from their molecular environment. Previous studies of the nucleotide‐dependent conformational changes of p97 were inconclusive. Here, we determined its structure in the presence of ADP, AMP‐PNP, or ATP‐γS at 6.1–7.4 Å resolution using single particle cryo‐electron microscopy. Both AAA domains, D1 and D2, assemble into essentially six‐fold symmetrical rings. The pore of the D1‐ring remains essentially closed under all nucleotide conditions, whereas the D2‐ring shows an iris‐like opening for ADP. The largest conformational changes of p97 are ‘swinging motions’ of the N‐terminal domains, which may enable segregation of ubiquitylated substrates from their environment.