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Purification of Human S100A12 and Its Ion-induced Oligomers for Immune Cell Stimulation
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Base molecular de la tetramerización inducida por Ca (II) y el secuestro de metales de transición en la calprotectina
Robert Silvers1,2, Jules R Stephan3, Robert G Griffin3,4
1Department of Chemistry & Biochemistry, Florida State University, Tallahassee, Florida 32306, United States.
Journal of the American Chemical Society
|October 26, 2021
Resumen
La calprotectina humana (CP) utiliza el calcio (Ca) para unirse a los metales y luchar contra los microbios. La unión de calcio cambia el CP entre estados inactivos y activos, lo que permite su función inmune al mejorar el secuestro de metales y la actividad antimicrobiana.
Área de la Ciencia:
- La bioquímica
- Inmunología
- Biología estructural
Sus antecedentes:
- La calprotectina humana (CP) es una proteína inmune innata clave involucrada en el secuestro de metales.
- La función antimicrobiana de CP se basa en la unión y autoasociación del calcio (Ca (II)).
- Faltaban datos estructurales sobre la forma apo del heterodímero de CP, lo que dificultaba la comprensión de su mecanismo de unión al metal.
Objetivo del estudio:
- Para aclarar los efectos estructurales y dinámicos de la unión de Ca (II) en el heterodímero αβ de la calprotectina humana (CP).
- Comprender cómo el enlace de Ca (II) facilita la transición de CP a un estado activo de secuestro de metales.
Principales métodos:
- Se utilizó la espectroscopia de resonancia magnética nuclear (RMN) en solución para estudiar el heterodímero CP αβ.
- Se analizaron los cambios estructurales y dinámicos en la unión de Ca (II).
Principales resultados:
- La unión de Ca (II) induce cambios conformacionales, favoreciendo un estado "activo" competente para la tetramerización.
- La unión de Ca (II) estabiliza el heterodímero αβ, promoviendo la formación del heterotetramero (αβ) 2.
- La unión de Ca (II) organiza los sitios críticos de unión de metales (His3Asp y His6) a través de efectos locales y alostéricos, incluida la estabilización de la hélice αIV en S100A9.
Conclusiones:
- La unión de Ca (II) es el desencadenante principal para la activación de CP y la función de secuestro de metales.
- El estudio revela el mecanismo molecular por el cual la CP responde al Ca (II) extracelular para la defensa del huésped.
- La comprensión de estas dinámicas estructurales proporciona información sobre la inmunidad innata y la homeostasis del metal.
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