6QS7

ClpB (DWB and K476C mutant) bound to casein in presence of ATPgammaS - state KC-2A

Summary for 6QS7

• Entry DOI: 10.2210/pdb6qs7/pdb
• EMDB information: 4621 4622 4623 4624 4625 4626
• Descriptor: Chaperone protein ClpB, casein, PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER, ... (5 entities in total)
• Functional Keywords: disaggregase, proteostasis, aaa, chaperone
• Biological source: Escherichia coli; More
• Total number of polymer chains: 7
• Total formula weight: 582163.44

Authors

Deville, C.,Saibil, H.R. (deposition date: 2019-02-20, release date: 2019-07-03, Last modification date: 2024-05-15)

Primary citation

Deville, C.,Franke, K.,Mogk, A.,Bukau, B.,Saibil, H.R.
Two-Step Activation Mechanism of the ClpB Disaggregase for Sequential Substrate Threading by the Main ATPase Motor.
Cell Rep, 27:3433-3446.e4, 2019

PubMed Abstract: AAA+ proteins form asymmetric hexameric rings that hydrolyze ATP and thread substrate proteins through a central channel via mobile substrate-binding pore loops. Understanding how ATPase and threading activities are regulated and intertwined is key to understanding the AAA+ protein mechanism. We studied the disaggregase ClpB, which contains tandem ATPase domains (AAA1, AAA2) and shifts between low and high ATPase and threading activities. Coiled-coil M-domains repress ClpB activity by encircling the AAA1 ring. Here, we determine the mechanism of ClpB activation by comparing ATPase mechanisms and cryo-EM structures of ClpB wild-type and a constitutively active ClpB M-domain mutant. We show that ClpB activation reduces ATPase cooperativity and induces a sequential mode of ATP hydrolysis in the AAA2 ring, the main ATPase motor. AAA1 and AAA2 rings do not work synchronously but in alternating cycles. This ensures high grip, enabling substrate threading via a processive, rope-climbing mechanism.

PubMed: 31216466
DOI: 10.1016/j.celrep.2019.05.075

Experimental method

ELECTRON MICROSCOPY (3.8 Å)