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El transportador truncado de glucosa del terminal C está bloqueado en una forma orientada hacia adentro sin actividad
1Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Nature
|June 7, 1990
Resumen
La alteración del transportador de glucosa GLUT1 mediante la eliminación de su dominio C-terminal lo hace inactivo. Esto sugiere que el dominio C-terminal es crucial para los cambios conformacionales y la función del transportador.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
Sus antecedentes:
- Los transportadores de glucosa facilitados, como GLUT1, son familias de proteínas con 12 dominios que abarcan la membrana.
- Un modelo de conformación alterna explica el mecanismo del transporte facilitado de glucosa.
- El papel del dominio intracelular C-terminal (término C) en la función de GLUT1 no se entiende completamente.
Objetivo del estudio:
- Para investigar la relación estructura-función del transportador GLUT1.
- Determinar el papel específico del dominio C-terminal intracelular en el transporte de glucosa mediado por GLUT1.
Principales métodos:
- Una deleción mutante del transportador GLUT1 del conejo fue diseñada utilizando ADN complementario (ADNc).
- El mutante carecía de 37 de los 42 aminoácidos del dominio C-terminal intracelular.
- El transportador mutante fue expresado en células de ovario de hámster chino (CHO).
Principales resultados:
- El mutante de deleción GLUT1 se expresó con éxito en la superficie celular de las células CHO.
- El transportador GLUT1 modificado no exhibió actividad de transporte de glucosa, lo que indica una inactivación funcional.
- Se supone que la pérdida de función es el resultado de una incapacidad para alterar la conformación.
Conclusiones:
- El dominio C-terminal intracelular de GLUT1 es esencial para su función de transporte.
- La eliminación del dominio C-terminal probablemente impide los cambios conformacionales necesarios para el transporte de glucosa.
- El dominio C-terminal de GLUT1 juega un papel crítico en el mantenimiento de la capacidad del transportador para cambiar entre las conformaciones orientadas hacia adentro y hacia afuera.
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