The central coupler of ClpXP controls intersubunit communication and couples intrasubunit chemical energy with force generation
Abstract
ClpX is a clockwise hexameric helical arrangement that hydrolyzes ATP to unfold proteins and translocate them into the proteolytic chamber. We investigate the central coupler, a three α-helix module conserved among AAA+ ATPases, which is proposed to enable intersubunit communication and mechanochemical coupling. Although fundamental in AAA+ ATPases, the molecular mechanism underlying these processes remains elusive in ClpX. By combining single-molecule optical tweezers, biochemical assays and single-particle cryo-EM we demonstrate that the central coupler, of the second-highest subunit of the ClpX clockwise helical arrangement, positions its Arginine-finger, sensor-I and sensor-II to contact the ATP of the anticlockwise neighbor subunit to trigger its hydrolysis. Then, the central coupler of the highest subunit rapidly couples the ATP hydrolysis with the downward motion of its substrate-translocating loop, enabling fast force generation to swiftly unfold protein substrates while maximizing the thermodynamic efficiency of the motor.
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BibTeX
@article{sosa2026central,
title = {{The central coupler of ClpXP controls intersubunit communication and couples intrasubunit chemical energy with force generation}},
author = {Robert P. Sosa and Alfredo Jose Florez Ariza and Jeonghoon Kim and Alexander B. Tong and Zhen-Hui Kang and Alicia Li and John Kuriyan and Carlos Bustamante},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78225-1},
url = {https://www.nature.com/articles/s41467-026-78225-1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The central coupler of ClpXP controls intersubunit communication and couples intrasubunit chemical energy with force generation
AU - Robert P. Sosa
AU - Alfredo Jose Florez Ariza
AU - Jeonghoon Kim
AU - Alexander B. Tong
AU - Zhen-Hui Kang
AU - Alicia Li
AU - John Kuriyan
AU - Carlos Bustamante
PY - 2026
DA - 2026/10/12
JO - Nature Communications
DO - 10.1038/s41467-026-78225-1
UR - https://www.nature.com/articles/s41467-026-78225-1
AB - ClpX is a clockwise hexameric helical arrangement that hydrolyzes ATP to unfold proteins and translocate them into the proteolytic chamber. We investigate the central coupler, a three α-helix module conserved among AAA+ ATPases, which is proposed to enable intersubunit communication and mechanochemical coupling. Although fundamental in AAA+ ATPases, the molecular mechanism underlying these processes remains elusive in ClpX. By combining single-molecule optical tweezers, biochemical assays and single-particle cryo-EM we demonstrate that the central coupler, of the second-highest subunit of the ClpX clockwise helical arrangement, positions its Arginine-finger, sensor-I and sensor-II to contact the ATP of the anticlockwise neighbor subunit to trigger its hydrolysis. Then, the central coupler of the highest subunit rapidly couples the ATP hydrolysis with the downward motion of its substrate-translocating loop, enabling fast force generation to swiftly unfold protein substrates while maximizing the thermodynamic efficiency of the motor.
SN - 2041-1723
ER -