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La estructura cristalina del transportador humano de glucosa GLUT1
Dong Deng1, Chao Xu1, Pengcheng Sun2
11] State Key Laboratory of Bio-membrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China [2] Center for Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China [3] Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China [4].
Nature
|May 23, 2014
Resumen
Los investigadores determinaron la estructura cristalina del transportador humano de glucosa GLUT1, revelando su conformación hacia adentro y abierta. Este avance ayuda a comprender el síndrome de deficiencia de GLUT1 y el pronóstico del cáncer.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Estructural Biología estructural.
- La medicina molecular es una medicina molecular.
Sus antecedentes:
- El transportador de glucosa 1 (GLUT1) facilita el transporte de glucosa en los eritrocitos y es crucial para el suministro de glucosa al cerebro y los órganos.
- Las mutaciones de GLUT1 causan el síndrome de deficiencia de GLUT1, y su sobreexpresión está relacionada con el pronóstico del cáncer.
- La estructura tridimensional del GLUT1 humano ha permanecido esquiva a pesar de una extensa investigación.
Objetivo del estudio:
- Para determinar la estructura cristalina de un GLUT humano de cuerpo entero1.1.
- Para aclarar el mecanismo de transporte de GLUT1 y su relación con las mutaciones asociadas a la enfermedad.
- Para comparar la estructura y el mecanismo de transporte de GLUT1 con otros transportadores.
Principales métodos:
- Se empleó cristalografía de rayos X para determinar la estructura del GLUT1 humano.
- La estructura se resolvió a una resolución de 3.2 Å.
- Se realizó un análisis basado en la estructura de las mutaciones asociadas a la enfermedad.
Principales resultados:
- La estructura cristalina de GLUT1 humano de cuerpo entero se determinó a una resolución de 3,2 Å.
- GLUT1 fue capturado en una conformación abierta hacia adentro, exhibiendo un pliegue canónico de la superfamilia de facilitadores mayores.
- La estructura facilita el mapeo de las mutaciones de la enfermedad y proporciona información mecanicista sobre la función de GLUT1.
Conclusiones:
- La estructura determinada de GLUT1 proporciona una base para la comprensión del síndrome de deficiencia de GLUT1 y las funciones de GLUT1 relacionadas con el cáncer.
- El análisis basado en la estructura ofrece información sobre el mecanismo de acceso alternado de GLUT1 y la subfamilia sugar porter.
- La comparación con homólogos bacterianos como XylE ayuda a comprender los mecanismos de transporte pasivo y activo.
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