Nucleotide-dependent conformational changes of the AAA+ ATPase p97 revisited

作者：Schuller Jan M; Beck Florian; Lossl Philip; Heck Albert J R; Foerster Friedrich

来源：FEBS LETTERS, 2016, 590(5): 595-604.

DOI：10.1002/1873-3468.12091

• AAA-ATPase
• Cdc48
• Cryo-EM
• ERAD
• protein quality control

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-gamma S at 6.1-7.4 angstrom 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.

• 出版日期2016-3