A KaiA Conformational Switch Links Day-Night Transitions to Clock Robustness
- 1Department of Chemistry & Biochemistry, University of California, Merced, CA, 95343, United States
Abstract
Biological clocks require mechanisms that enable transition between temporal phases and buffer against environmental fluctuations. In the cyanobacterial KaiABC-based circadian oscillator, KaiA has been regarded as a daytime activator that is passively sequestered at night. Here we define KaiA as a conformationally regulated activator and an active catalyst of the night-to-dawn transition. We identify a single linker helix, 5, that acts as a structural switch, mediating a domain-driven "tug-of-war" that sets the open-closed equilibrium in KaiA. Structure-guided mutations that shift this balance in either direction abolish stable rhythmicity both in vitro and in cells. Also, we show that substoichiometric KaiA dismantles nighttime KaiB-KaiC complexes through interactions with the KaiC C-terminal tails and likely initiates an autocatalytic feedback loop that resets the phosphorylation cycle at dawn. Furthermore, we present two independent kinetic models that offer distinct, deterministic explanations for the clock's low-temperature amplitude decline and failure at 20 {degrees} C.
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BibTeX
@misc{chandradasan2026kaia,
title = {{A KaiA Conformational Switch Links Day-Night Transitions to Clock Robustness}},
author = {A. C. Chandradasan and A. Taton and A. G. Chavan and N. Zhang and C. A. Omaga and A. A. Gonzalez Crespo and L. M. Vasquez Perez and L. F. Larrondo and M. Fang and S. S. Golden and A. LiWang},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.13.758887},
url = {https://www.biorxiv.org/content/10.64898/2026.10.13.758887v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - A KaiA Conformational Switch Links Day-Night Transitions to Clock Robustness
AU - A. C. Chandradasan
AU - A. Taton
AU - A. G. Chavan
AU - N. Zhang
AU - C. A. Omaga
AU - A. A. Gonzalez Crespo
AU - L. M. Vasquez Perez
AU - L. F. Larrondo
AU - M. Fang
AU - S. S. Golden
AU - A. LiWang
PY - 2026
DA - 2026/10/13
PB - bioRxiv
DO - 10.64898/2026.10.13.758887
UR - https://www.biorxiv.org/content/10.64898/2026.10.13.758887v1
AB - Biological clocks require mechanisms that enable transition between temporal phases and buffer against environmental fluctuations. In the cyanobacterial KaiABC-based circadian oscillator, KaiA has been regarded as a daytime activator that is passively sequestered at night. Here we define KaiA as a conformationally regulated activator and an active catalyst of the night-to-dawn transition. We identify a single linker helix, 5, that acts as a structural switch, mediating a domain-driven "tug-of-war" that sets the open-closed equilibrium in KaiA. Structure-guided mutations that shift this balance in either direction abolish stable rhythmicity both in vitro and in cells. Also, we show that substoichiometric KaiA dismantles nighttime KaiB-KaiC complexes through interactions with the KaiC C-terminal tails and likely initiates an autocatalytic feedback loop that resets the phosphorylation cycle at dawn. Furthermore, we present two independent kinetic models that offer distinct, deterministic explanations for the clock's low-temperature amplitude decline and failure at 20 {degrees} C.
ER -