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El dinucleótido cíclico c-di-AMP es un regulador alostérico de la función de la enzima metabólica
Kamakshi Sureka1, Philip H Choi2, Mimi Precit1
1Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
Cell
|September 13, 2014
Resumen
El monofosfato cíclico de di-adenosina (c-di-AMP) es vital para el crecimiento bacteriano. Este estudio revela que el c-di-AMP regula el metabolismo bacteriano al unirse a la piruvato carboxilasa, lo que afecta la infección.
Área de la Ciencia:
- Microbiología Microbiología.
- Biología Molecular Biología Molecular
- La bioquímica es la bioquímica.
Sus antecedentes:
- El monofosfato cíclico de di-adenosina (c-di-AMP) es un segundo mensajero crucial en las bacterias, esencial para el crecimiento y la infección.
- Los mecanismos moleculares precisos que rigen las vías de señalización de c-di-AMP siguen siendo en gran parte sin esclarecer.
Objetivo del estudio:
- Para identificar nuevas proteínas que interactúan con c-di-AMP en Listeria monocytogenes.
- Para aclarar el papel regulador de c-di-AMP en el metabolismo bacteriano y la infección.
Principales métodos:
- Pantalla de proteomía química para identificar las proteínas de unión a c-di-AMP.
- Análisis bioquímicos y cristalografía de rayos X para caracterizar las interacciones proteína-ligando.
- Manipulación genética para evaluar el impacto del agotamiento de c-di-AMP en la fisiología bacteriana y la infección.
Principales resultados:
- La piruvato carboxilasa (LmPC) fue identificada como un receptor c-di-AMP en Listeria monocytogenes.
- Se caracterizó un nuevo sitio regulador alostérico en LmPC, distinto del sitio activo, que media la unión a c-di-AMP e influye en la actividad catalítica.
- La interrupción de la unión de c-di-AMP al LmPC condujo a una desregulación metabólica, lo que afectó el crecimiento bacteriano, la lisis y la carga de infecciones.
Conclusiones:
- Este estudio revela un papel no reconocido previamente para el c-di-AMP en la regulación del metabolismo bacteriano central a través de la piruvato carboxilasa.
- Los hallazgos amplían el repertorio conocido de vías de señalización de c-di-AMP y resaltan su importancia en la patogénesis bacteriana.
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