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Mecanismo de señalización transmembrana por las quinasas de histidina de los sensores
Ivan Gushchin1,2, Igor Melnikov3, Vitaly Polovinkin4,2,5
1Institute of Complex Systems (ICS), ICS-6: Structural Biochemistry, Research Centre Jülich, 52425 Jülich, Germany. ivan.gushchin@phystech.edu valentin.gordeliy@ibs.fr.
Science (New York, N.Y.)
|May 20, 2017
Resumen
Las quinasas sensoriales de histidina son receptores transmembranales vitales. Revelamos sus mecanismos estructurales, mostrando cómo la unión de ligandos desencadena los desplazamientos y rotaciones de la hélice, avanzando en la comprensión de los sistemas de señalización de dos componentes.
Área de la Ciencia:
- Microbiología y Biología Molecular
- Biología estructural
- La bioquímica
Sus antecedentes:
- Los receptores de transmembrana (TM), específicamente las sensoras de histidina quinasa, son cruciales para los sistemas de señalización de dos componentes (TCS) en todos los dominios de la vida.
- Los mecanismos estructurales detallados que rigen la señalización TM en estos receptores esenciales permanecen en gran medida sin aclarar.
- Comprender estos mecanismos es vital para descifrar la comunicación celular y desarrollar nuevas estrategias terapéuticas.
Objetivo del estudio:
- Elucidar los mecanismos estructurales de la transducción de señales en las quinasas de histidina de los sensores transmembrana.
- Para proporcionar estructuras cristalinas de alta resolución del sensor de nitrato y nitrito de Escherichia coli NarQ.
- Investigar los cambios conformacionales inducidos por la unión de ligandos y su impacto en la señalización.
Principales métodos:
- Se empleó la cristalografía de rayos X para determinar las estructuras del sensor periplásmico, TM y los dominios HAMP citoplasmáticos de NarQ.
- Las estructuras se resolvieron tanto para los estados ligand-unidos como para los mutados ligand-libres del sensor NarQ.
- El análisis se centró en los movimientos de dominio y la comunicación entre dominios durante la transducción de señales.
Principales resultados:
- Las estructuras cristalinas revelaron reordenamientos inducidos por ligandos y desplazamientos similares a los pistones dentro de las hélices TM de NarQ.
- El dominio HAMP citoplasmático exhibió movimientos similares a palancas, convirtiendo efectivamente los movimientos del pistón de la hélice TM en rotaciones helicoidales.
- Estos hallazgos proporcionan una base estructural detallada para la transmisión de señales a través de la membrana en los TCS.
Conclusiones:
- El estudio proporciona un marco estructural completo para la comprensión de la señalización transmembrana de dos componentes.
- Los mecanismos aclarados ofrecen información sobre cómo se transducen las señales ambientales a través de la membrana celular.
- Estos hallazgos allanan el camino para el diseño racional de tratamientos antimicrobianos dirigidos a los TCS.
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