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Estructura cristalina de un transportador de nucleósidos concentrados de Vibrio cholerae a 2,4 Å
Zachary Lee Johnson1, Cheom-Gil Cheong, Seok-Yong Lee
1Department of Biochemistry and Ion Channel Research Unit, Duke University Medical Center, 2 Genome Court, Durham, North Carolina 27710, USA.
Nature
|March 13, 2012
Resumen
Los transportadores de nucleósidos (NTs) mueven nucleósidos esenciales y fármacos a través de las membranas celulares. Este estudio revela la estructura cristalina de un transportador de nucleósidos concentrativo bacteriano, explicando su mecanismo dependiente de iones de sodio para la absorción de nucleósidos.
Área de la Ciencia:
- Biología Estructural Biología estructural.
- Transporte de la membrana Transporte de la membrana
- La bioquímica es la bioquímica.
Sus antecedentes:
- Los nucleósidos son vitales para la síntesis de ADN / ARN y la señalización celular.
- Los transportadores de nucleósidos (NT) facilitan el transporte de fármacos derivados de nucleósidos y nucleósidos a través de las membranas celulares.
- Los transportadores de nucleósidos concentrados (SLC28) utilizan gradientes iónicos para el transporte activo, pero su base estructural es desconocida.
Objetivo del estudio:
- Determinar la base estructural del transporte de nucleósidos acoplados a iones por transportadores de nucleósidos concentrados.
- Aclarar el mecanismo del transporte de fármacos derivados de nucleósidos y nucleósidos a través de las membranas celulares.
Principales métodos:
- Cristalografía de rayos X de un transportador de nucleósidos concentrados de Vibrio cholerae con uridina a una resolución de 2.4 Å.
- Pruebas funcionales para confirmar la dependencia del gradiente de iones de sodio.
Principales resultados:
- La estructura cristalina revela la arquitectura de los transportadores de nucleósidos concentrados.
- Determinantes moleculares identificados para la unión de nucleósidos y sodio.
- Se ha demostrado el transporte de nucleósidos dependiente del gradiente de iones de sodio, similar a los ortólogos humanos.
Conclusiones:
- La estructura proporciona un marco para comprender los mecanismos de transporte de fármacos nucleósidos y nucleósidos.
- Las ideas sobre la arquitectura del transportador y el acoplamiento iónico son cruciales para el desarrollo de fármacos dirigidos a los NT.
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