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Biología estructural. Bases estructurales para el reconocimiento de quimiocinas y la activación de un receptor

John S Burg¹, Jessica R Ingram², A J Venkatakrishnan³

¹Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.

Science (New York, N.Y.)

|March 7, 2015

Resumen

Los investigadores visualizaron la estructura de un receptor de quimioquina viral (GPCR) unido a una quimioquina humana. Esto revela cómo las GPCR virales pueden permanecer activas sin señales externas, impactando las estrategias de evasión inmune.

Área de la Ciencia:

Biología Estructural Biología estructural.
Virología Virología.
Inmunología Inmunología.

Sus antecedentes:

Las quimiocinas son moduladores inmunes que activan los receptores acoplados a proteínas G (GPCR).
Los virus utilizan quimiocinas y sus receptores para interrumpir la inmunidad del huésped.
El mecanismo de activación del ligando proteico de los GPCR no se comprende completamente.

Objetivo del estudio:

Para determinar la estructura de un receptor de quimioquina viral unido a un ligando de quimioquina.
Para dilucidar la base molecular de la activación viral de GPCR y la evasión inmune.

Principales métodos:

Cristalografía de rayos X con una resolución de 2,9 angstroms.
Formación de complejo entre el citomegalovirus humano GPCR US28 y el dominio de quimioquina CX3CL1 (fractalquina).
Simulaciones moleculares a nivel atómico.

Principales resultados:

La estructura cristalina revela el modo de unión de CX3CL1 al receptor US28.
El receptor US28 adopta una conformación similar al estado activo.
Las simulaciones sugieren que una desestabilización intrínseca del estado inactivo contribuye a la actividad de US28.

Conclusiones:

La estructura proporciona una visión a nivel atómico de las interacciones virales GPCR-quimioquina.
Los GPCR virales pueden poseer mecanismos inherentes para la actividad constitutiva, ayudando a la subversión inmune.
Comprender estas interacciones es crucial para desarrollar terapias antivirales dirigidas.

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