Atomic-resolution monitoring of protein maturation in live human cells by NMR

Lucia Banci, Letizia Barbieri, Ivano Bertini, Enrico Luchinat, Erica Secci, Yuguang Zhao & A Radu Aricescu.

We use NMR directly in live human cells to describe the complete post-translational maturation process of human superoxide dismutase 1 (SOD1). We follow, at atomic resolution, zinc binding, homodimer formation and copper uptake, and discover that copper chaperone for SOD1 oxidizes the SOD1 intrasubunit disulfide bond through both copper-dependent and copper-independent mechanisms. Our approach represents a new strategy for structural investigation of endogenously expressed proteins in a physiological (cellular) environment.

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