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Transferencia de fósforo y oclusión de iones de calcio en la bomba de calcio
Thomas Lykke-Møller Sørensen1, Jesper Vuust Møller, Poul Nissen
1Department of Molecular Biology, University of Aarhus, Gustav Wieds Vej 10C, DK-8000 Aarhus C, Denmark.
Science (New York, N.Y.)
|June 12, 2004
Resumen
Los investigadores revelan cómo el retículo sarco-endo-plasmático Ca2+-adenosina trifosfatasa (SERCA) utiliza el trifosfato de adenosina (ATP) para bombear iones de calcio. Las ideas estructurales muestran que la unión de ATP desencadena cambios conformacionales que permiten un transporte eficiente de calcio y evitan el reflujo.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Estructural Biología estructural.
- Fisiología Molecular Fisiología Molecular
Sus antecedentes:
- La Ca2+-adenosina trifosfatasa (SERCA) del retículo sarco-endo) plasmático es crucial para la contracción muscular y la homeostasis del calcio celular.
- El mantenimiento de un estrecho acoplamiento entre la hidrólisis del trifosfato de adenosina (ATP) y el transporte vectorial de iones es esencial para las bombas iónicas que consumen ATP.
Objetivo del estudio:
- Para aclarar los mecanismos estructurales de la interacción de SERCA con ATP y su papel en el transporte de calcio.
- Comprender los cambios conformacionales involucrados en el ciclo catalítico SERCA.
Principales métodos:
- Se determinaron dos estructuras cristalinas de SERCA ligado a Ca2+ a una resolución de 2,6 y 2,9 angstroms.
- Se utilizó un análogo de ATP no hidrolizable [adenosina (metileno beta-gamma) trifosfato] y difosfato de adenosina más fluoruro de aluminio.
Principales resultados:
- SERCA revelado reacciona con ATP a través de un mecanismo asociativo que involucra dos iones Mg2+, formando un intermediario aspartil-fosforilado (Ca2-E1 aproximadamente P).
- Se observó que la unión de ATP induce cambios conformacionales, tirando de las hélices transmembranares 1 y 2.
- Se demostró que estos cambios cierran la entrada de Ca2+ citosólico, evitando el reflujo antes de la liberación de iones.
Conclusiones:
- El estudio proporciona evidencia estructural de alta resolución para el mecanismo del transporte de calcio mediado por ATP por SERCA.
- Estos hallazgos mejoran nuestra comprensión de la función de la bomba iónica y la base estructural de la regulación del calcio.
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