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Estructura cristalina del transportador de esteroles humanos ABCG5/ABCG8

Jyh-Yeuan Lee¹, Lisa N Kinch^2,3,4, Dominika M Borek^2,3

¹Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.

|May 5, 2016

Resumen

La estructura del transportador G5/G8 de la cinta de unión ATP (ABC) revela cómo se excretan los esteroles. Este hallazgo proporciona un marco para la comprensión de la sitosterolemia, un trastorno causado por mutaciones del transportador.

Área de la Ciencia:

La bioquímica
Biología molecular
Biología estructural

Sus antecedentes:

Los transportadores de cassette de unión de ATP (ABC) son cruciales para mantener el equilibrio de esteroles en los eucariotas.
El heterodímero ABCG5/ABCG8 (G5G8) facilita la excreción de esteroles neutros en el hígado y los intestinos.
Las mutaciones en G5G8 conducen a la sitosterolemia, caracterizada por la acumulación de esteroles y la aterosclerosis temprana.

Objetivo del estudio:

Para determinar la estructura atómica del transportador de esteroles humano G5G8.
Proporcionar una comprensión mecánica del transporte de esteroles y el impacto de las mutaciones causantes de enfermedades.

Principales métodos:

Cristalografía de rayos X de G5G8 humano reconstituido en bicapas de lípidos.
Determinación de la estructura libre de nucleótidos a una resolución de 3,9 Å.

Principales resultados:

Se generó el primer modelo atómico de un transportador de esteroles ABC.
Se identificó un nuevo pliegue transmembranar, compartido por diversos transportadores ABC.
Las redes de interacciones que acoplan los dominios de transmembrana y unión de nucleótidos revelan una asimetría catalítica.

Conclusiones:

La estructura G5G8 aclara el mecanismo de transporte de esteroles.
Esta visión estructural ofrece un marco para comprender la sitosterolemia y los trastornos relacionados.
Los hallazgos tienen implicaciones para la superfamilia de transportadores ABC.

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