TY  - JOUR
AU  - Pesce, Luca
AU  - Calandrini, Vania
AU  - Marjault, Henri-Baptiste
AU  - Lipper, Colin H.
AU  - Rossetti, Giulia
AU  - Mittler, Ron
AU  - Jennings, Patricia Ann
AU  - Nechushtai, Rachel
AU  - Carloni, Paolo
AU  - Bauer, Andreas
TI  - Molecular Dynamics Simulations of the [2Fe-2S] Cluster-Binding Domain of NEET Proteins Reveal Key Molecular Determinants That Induce Their Cluster Transfer/Release
JO  - The journal of physical chemistry  / B
VL  - 121
IS  - 47
SN  - 1520-5207
CY  - Washington, DC
PB  - Soc.
M1  - FZJ-2017-07352
SP  - 10648–10656
PY  - 2017
AB  - 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.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000417228600006
DO  - DOI:10.1021/acs.jpcb.7b10584
UR  - https://juser.fz-juelich.de/record/838842
ER  -