ausblenden:
Schlagwörter:
VALOSIN-CONTAINING PROTEIN; MASS ANALYSIS; CRYO-EM; P97/VCP; REVEALS;
COMMUNICATION; ASSEMBLIES; PROTEASOME; MICROSCOPY; RESOLUTIONAAA-ATPase; Cdc48; Cryo-EM; ERAD; protein quality control;
Zusammenfassung:
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.
