La unión del cobre a la forma N-terminalmente acetilada y natural de la alfa-sinucleína induce el plegamiento helicoidal local

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Structure and Coordination Determination of Peptide-metal Complexes Using 1D and 2D 1H NMR

Structure and Coordination Determination of Peptide-metal Complexes Using 1D and 2D 1H NMR

Published on: December 16, 2013

Marco C Miotto, Ariel A Valiente-Gabioud, Giulia Rossetti¹

¹§Computational Biophysics, German Research School for Simulation Sciences and Computational Biomedicine, Institute for Advanced Simulations IAS-5, Forschungszentrum Jülich, D-52425 Jülich, Germany.

Journal of the American Chemical Society

|May 5, 2015

Resumen

Las interacciones del cobre cerebral (Cu(I)) con la alfa-sinucleína acetilada (AcAS) están relacionadas con la enfermedad de Parkinson (EP). Este estudio revela que la formación del complejo AcAS-Cu(I) estabiliza la estructura de AcAS, afectando potencialmente la patogénesis de la EP.

Área de la Ciencia:

La neurociencia es la neurociencia.
La bioquímica es la bioquímica.
Biología Estructural Biología estructural.

Sus antecedentes:

La enfermedad de Parkinson (EP) está relacionada con la homeostasis del cobre en el cerebro y la agregación de alfa-sinucleína (AS).
La forma fisiológica de AS es N-terminalmente acetilado (AcAS).

Objetivo del estudio:

Caracterizar estructuralmente la interacción entre el cobre (Cu) y la alfa-sinucleína acetilada (AcAS).
Comprender el impacto de la unión de Cu(I) en la conformación y motilidad de AcAS.

Principales métodos:

Se empleó la espectroscopia de Resonancia Magnética Nuclear (RMN) para estudiar las interacciones Cu(I) -AcAS.

Principales resultados:

Se observó la formación de un complejo AcAS-Cu (I) en la región N-terminal.
El complejo AcAS-Cu(I) estabiliza las conformaciones locales, induciendo una estructura secundaria α-helical.
Se detectó motilidad restringida en la región N-terminal tras la formación de complejos.

Conclusiones:

Esta investigación proporciona nuevos conocimientos sobre la metalobiología de la enfermedad de Parkinson.
La formación del complejo AcAS-Cu(I) puede influir en la unión y agregación de la membrana AcAS, procesos clave en la EP.
Abre nuevas vías para investigar la patogénesis de la EP y los posibles objetivos terapéuticos.

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