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Desde los relojes primordiales hasta los osciladores circadianos
Warintra Pitsawong1,2, Ricardo A P Pádua1, Timothy Grant3,4,5
1Howard Hughes Medical Institute and Department of Biochemistry, Brandeis University, Waltham, MA, USA.
Nature
|March 23, 2023
Resumen
Este estudio revela el antiguo mecanismo del reloj circadiano KaiBC en Rhodobacter sphaeroides, identificando la relación ATP-ADP como la clave ambiental que impulsa este reloj biológico primordial.
Área de la Ciencia:
- La bioquímica
- Biología molecular
- Cronología
Sus antecedentes:
- Los ritmos circadianos son procesos biológicos fundamentales regulados por los osciladores después de la traducción.
- El sistema KaiABC es un reloj circadiano cianobacteriano bien entendido, pero los antiguos sistemas solo KaiBC siguen sin caracterizarse en gran medida.
- Se supone que estos sistemas KaiBC poseen un mecanismo básico de cronometraje similar al reloj de arena.
Objetivo del estudio:
- Para investigar el reloj circadiano primordial en Rhodobacter sphaeroides, que utiliza sólo las proteínas KaiBC.
- Para aclarar los mecanismos moleculares de este antiguo sistema de cronometraje en ausencia de KaiA.
- Para entender los orígenes evolutivos de los osciladores circadianos.
Principales métodos:
- Se empleó cristalografía de rayos X y microscopía electrónica criogénica para determinar la estructura de KaiC.
- Se realizó un análisis cinético para identificar señales ambientales y comprender la dinámica del reloj.
- Se integraron datos estructurales y cinéticos para mapear las redes alostéricas dentro de la proteína KaiC.
Principales resultados:
- Se descubrió un nuevo pliegue dodecamérico para KaiC, que comprende dos hexámeres unidos por un haz de bobina en espiral de 12 hélices.
- Esta interacción entre bobina y bobina, mediada por la extensión carboxiterminal KaiC, representa un antiguo elemento regulador.
- Se identificó una red alostérica de largo alcance que conecta los cambios conformacionales con los sitios de fosforilación.
- La proporción de ATP a ADP fue identificada como la señal ambiental que impulsa el ciclo diario del reloj.
Conclusiones:
- El sistema KaiBC en Rhodobacter sphaeroides funciona como un oscilador circadiano primordial.
- La estructura dodecamérica identificada de KaiC y su regulación alostérica proporcionan información sobre la evolución de los relojes circadianos.
- Las fluctuaciones ambientales de ATP a ADP son la fuerza impulsora detrás de este antiguo reloj biológico, que ofrece una visión de los primeros mecanismos de cronometraje.
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