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El dominio octarepetado de la proteína priónica se une a Cu (II) con tres modos de coordinación distintos a un pH de
Madhuri Chattopadhyay1, Eric D Walter, Dustin J Newell
1Department of Chemistry & Biochemistry, University of California, Santa Cruz, California 95064, USA.
Journal of the American Chemical Society
|September 8, 2005
Resumen
La proteína priónica (PrP) se une a los iones de cobre (Cu2+) a través de su dominio octarepetado. Este estudio revela tres modos distintos de coordinación del cobre a un pH de 7.4, lo que aclara el PrP.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Estructural Biología estructural.
- Química bioorgánica Química bioorgánica.
Sus antecedentes:
- El dominio octarepetado N-terminal de la proteína priónica se une a los iones Cu2+.
- La secuencia de repetición fundamental es PHGGGWGQ.
- Estudios anteriores indicaron que la ocupación total de cobre implica que cada segmento de HGGGW se une a un Cu2+.
Objetivo del estudio:
- Investigar los modos de coordinación del cobre en el dominio octarepetado de la proteína priónica con baja ocupación de cobre.
- Para explorar la posible participación de los residuos de histidina en la coordinación alternativa.
- Para caracterizar los cambios estructurales dependientes del cobre en el dominio octarepetado.
Principales métodos:
- Utilizó resonancia paramagnética de electrones de banda X (EPR), EPR de banda S y modulación de la envolvente de eco de espín de electrones (ESEEM).
- Empleó una biblioteca de péptidos modificados para favorecer interacciones específicas de coordinación.
- Se analizaron los modos de coordinación del cobre a pH 7.4.4.
Principales resultados:
- Identificó y caracterizó completamente tres modos distintos de coordinación del cobre a un pH de 7.4.
- Se confirmó la coordinación múltiple de histidina en estequiometría baja en cobre.
- Se detectaron interacciones cobre-cobre a plena ocupación, lo que sugiere el colapso del dominio y la absorción cooperativa de cobre.
Conclusiones:
- Proporciona la primera caracterización completa de los modos de coordinación dominantes del cobre en el dominio octarepetado de PrP a pH 7.4.4.
- Elucida la base estructural para la unión del cobre a través de diferentes concentraciones de cobre.
- Destaca el papel de la coordinación de la histidina en entornos bajos en cobre y el colapso del dominio en entornos altos en cobre.
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