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PIP-on-a-chip: A Label-free Study of Protein-phosphoinositide Interactions
Published on: July 27, 2017
Pb2+ como modulador de las interacciones proteína-membrana
Krystal A Morales1, Mauricio Lasagna, Alexey V Gribenko
1Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843, USA.
Journal of the American Chemical Society
|May 28, 2011
Resumen
El plomo (Pb2+) se une al dominio C2α de la proteína cinasa Cα (PKCα) con mayor afinidad que el calcio (Ca2+), afectando su unión a la membrana y contribuyendo potencialmente a la toxicidad del plomo.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Toxicología Toxicología.
- Biología Estructural Biología estructural.
Sus antecedentes:
- El plomo (Pb2+) es una toxina ambiental que imita los iones metálicos divalentes esenciales.
- Los mecanismos moleculares subyacentes a la toxicidad del plomo no se comprenden completamente.
- La proteína quinasa Cα (PKCα) es un objetivo molecular conocido del plomo.
Objetivo del estudio:
- Investigar los efectos estructurales y de unión a la membrana de Pb2+ en el dominio C2α de PKCα.
- Para dilucidar las interacciones moleculares entre Pb2+ y C2α.
Principales métodos:
- La espectroscopia de resonancia magnética nuclear (RMN) también se conoce como espectroscopia de resonancia magnética nuclear.
- Calorimetría de titulación isotérmica (ITC, por sus siglas en inglés)
- Cristalografía de rayos X con rayos X.
- La espectroscopia de transferencia de energía de resonancia Förster (FRET)
Principales resultados:
- C2α se une a Pb2+ con mayor afinidad que Ca2+.
- Las estructuras cristalinas revelaron que la coordinación Pb2 + requiere la rotación de la cadena lateral, con geometrías holodireccionadas y hemidireccionadas coexistentes.
- Pb2+ desplaza a Ca2+ de C2α y compite por los sitios de unión a la membrana en las bicapas lipídicas.
Conclusiones:
- La interacción de Pb2+ con C2α difiere significativamente de la de Ca2+.
- La unión de Pb2+ a C2α y su competencia por los sitios de la membrana probablemente contribuyen a la inhibición de PKCα y la toxicidad por plomo.
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