Regulation of a Classical Allosteric Molecular Machine by an Intrinsically Disordered Domain: the C-termini of GroEL
- 1Texas A & M University
Abstract
The bacterial chaperonin GroEL is a canonical example of an ATP-dependent molecular machine that must couple ligand binding to productive conformational work. GroEL passes through a series of distinct structural shifts, driven by ATP binding and hydrolysis, which power a facilitated protein folding reaction. How the complex allostery of the GroEL oligomer creates a folding cycle that is both efficient and directional remains incompletely understood. Here, we combine variable-temperature native ion mass spectrometry with single-molecule FRET to examine how the intrinsically disordered, highly conserved GroEL C-terminal tails impact the allosteric behavior of a single GroEL ring. Our observations show that the C-terminal tails restrain the conformational dynamics of the GroEL ring, most likely through direct interactions with the upper apical domains of the GroEL subunits, a constraint that is progressively released as ATP binds. These results support a model in which the C-terminal tails act as an entropic regulator of the GroEL reaction cycle: transient interactions between the tails and GroEL apical domains restrain premature ring opening and tune the energetic threshold for productive engagement by the smaller GroES co-chaperonin. By linking disordered tail dynamics to the classically cooperative reorganization of the GroEL ring, this mechanism enforces an ordered allosteric cascade that minimizes wasteful formation of empty GroEL-GroES cavities. These findings reveal how the conformational properties of an intrinsically disordered element can be exploited to optimize the energetic efficiency and functional timing of a large allosteric machine.
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BibTeX
@misc{powers2026regulation,
title = {{Regulation of a Classical Allosteric Molecular Machine by an Intrinsically Disordered Domain: the C-termini of GroEL}},
author = {M. E. Powers and K. A. Evans and H. Sun and D. H. Russell and H. S. Rye},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.01.748644},
url = {https://www.biorxiv.org/content/10.64898/2026.09.01.748644v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Regulation of a Classical Allosteric Molecular Machine by an Intrinsically Disordered Domain: the C-termini of GroEL
AU - M. E. Powers
AU - K. A. Evans
AU - H. Sun
AU - D. H. Russell
AU - H. S. Rye
PY - 2026
DA - 2026/09/01
PB - bioRxiv
DO - 10.64898/2026.09.01.748644
UR - https://www.biorxiv.org/content/10.64898/2026.09.01.748644v1
AB - The bacterial chaperonin GroEL is a canonical example of an ATP-dependent molecular machine that must couple ligand binding to productive conformational work. GroEL passes through a series of distinct structural shifts, driven by ATP binding and hydrolysis, which power a facilitated protein folding reaction. How the complex allostery of the GroEL oligomer creates a folding cycle that is both efficient and directional remains incompletely understood. Here, we combine variable-temperature native ion mass spectrometry with single-molecule FRET to examine how the intrinsically disordered, highly conserved GroEL C-terminal tails impact the allosteric behavior of a single GroEL ring. Our observations show that the C-terminal tails restrain the conformational dynamics of the GroEL ring, most likely through direct interactions with the upper apical domains of the GroEL subunits, a constraint that is progressively released as ATP binds. These results support a model in which the C-terminal tails act as an entropic regulator of the GroEL reaction cycle: transient interactions between the tails and GroEL apical domains restrain premature ring opening and tune the energetic threshold for productive engagement by the smaller GroES co-chaperonin. By linking disordered tail dynamics to the classically cooperative reorganization of the GroEL ring, this mechanism enforces an ordered allosteric cascade that minimizes wasteful formation of empty GroEL-GroES cavities. These findings reveal how the conformational properties of an intrinsically disordered element can be exploited to optimize the energetic efficiency and functional timing of a large allosteric machine.
ER -