Structural Variations of Metallothionein with or without Zinc Ions Elucidated by All-Atom Molecular Dynamics Simulations

Metallothionein (MT) is a small globular protein that binds to trace metals. However, it was still unclear how the existence of metal ions affects the structure of MT. Therefore, we performed all-atom molecular dynamics (MD) simulations under several surrounding conditions with or without Zn2+ ions. As a result of 10 μs MD simulation, MT without Zn2+ ions tended to adopt an extended β-hairpin structure, while MT with Zn2+ ions became a globular structure like the NMR structure. Furthermore, we also found that the capture of Zn2+ ions by the second and third cysteines played a crucial role in the formation of the native structure. The finding of the Zn2+ binding for the specific cysteines and the unknown β-hairpin structure will provide new insights into the structural mechanism of metal signaling.