%0 Journal Article
%A Pesce, Luca
%A Calandrini, Vania
%A Marjault, Henri-Baptiste
%A Lipper, Colin H.
%A Rossetti, Giulia
%A Mittler, Ron
%A Jennings, Patricia Ann
%A Nechushtai, Rachel
%A Carloni, Paolo
%A Bauer, Andreas
%T Molecular Dynamics Simulations of the [2Fe-2S] Cluster-Binding Domain of NEET Proteins Reveal Key Molecular Determinants That Induce Their Cluster Transfer/Release
%J The journal of physical chemistry  / B
%V 121
%N 47
%@ 1520-5207
%C Washington, DC
%I Soc.
%M FZJ-2017-07352
%P 10648–10656
%D 2017
%X The NEET proteins are a novel family of iron-sulfur proteins characterized by an unusual 3 cysteine and one histidine coordinated [2Fe-2S] cluster. Aberrant cluster release, dictated by the breakage of the Fe-N bond, is implicated in a variety of human diseases, including cancer and neurodegenerative diseases. Here molecular dynamics in the multi-μs timescale, along with quantum chemical calculations, on two representative members of the family (the human NAF-1 and mitoNEET proteins) show that the loss of the cluster is associated with a dramatic decrease of secondary and tertiary structure. In addition, the calculations provide a mechanism for cluster release and clarify, for the first time, crucial differences existing between the two proteins, which are reflected in the experimentally observed difference in pH-dependent cluster reactivity. The reliability of our conclusions is established by an extensive comparison with NMR data of the proteins in solution, in part measured in this work.
%F PUB:(DE-HGF)16
%9 Journal Article
%U <Go to ISI:>//WOS:000417228600006
%R 10.1021/acs.jpcb.7b10584
%U https://juser.fz-juelich.de/record/838842