Extended Data Fig. 10: Expanded model of the complete cycle of substrate processing by the human 26S proteasome.
From: Cryo-EM structures and dynamics of substrate-engaged human 26S proteasome
The cartoon summarizes the concept of three principal modes of coordinated ATP hydrolysis observed in the seven states and our proposal of how they regulate the complete cycle of substrate processing by the proteasome holoenzyme. Coordinated ATP hydrolysis in modes 1, 2 and 3 features hydrolytic events in two oppositely positioned ATPases11,36, in two consecutive ATPases9,37,38, and in only one ATPase at a time39,40,43,44,45,46, respectively. Substrate processing undergoes three major steps before CP gate opening for processive translocation: (1) ubiquitin recognition; (2) simultaneous deubiquitylation and substrate engagement with the AAA-ATPase ring; and (3) translocation initiation, which involves multiple simultaneous events, including ubiquitin release, ATPase repositioning and switching of the RPT C-tail insertion pattern. In some cases, the initiation of translocation may precede deubiquitylation. In steps 1 and 2, the ATPases follow mode-1 ATP hydrolysis. In step 3, they follow mode-2 ATP hydrolysis. After the gate is open, the AAA-ATPases hydrolyse ATP in mode 3, in which only one nucleotide is hydrolysed at a time.
