Journal Article

FZJ-2017-07352

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Molecular Dynamics Simulations of the [2Fe-2S] Cluster-Binding Domain of NEET Proteins Reveal Key Molecular Determinants That Induce Their Cluster Transfer/Release

Pesce, L.FZJ* ; Calandrini, V.FZJ* ; Marjault, H.-B. ; Lipper, C. H. ; Rossetti, G.FZJ* ; Mittler, R. ; Jennings, P. A. ; Nechushtai, R. ; Carloni, P. (Corresponding author)FZJ* ; Bauer, A.FZJ*

2017
Soc. Washington, DC

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Please use a persistent id in citations: http://hdl.handle.net/2128/16255  doi:10.1021/acs.jpcb.7b10584

Abstract: 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.

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Contributing Institute(s):

1. Computational Biomedicine (IAS-5)
2. Computational Biomedicine (INM-9)
3. JARA - HPC (JARA-HPC)
4. Jülich Supercomputing Center (JSC)
5. Molekulare Organisation des Gehirns (INM-2)

Research Program(s):

1. 574 - Theory, modelling and simulation (POF3-574) (POF3-574)
2. 511 - Computational Science and Mathematical Methods (POF3-511) (POF3-511)
3. Predicting the apo-structure of a NEET protein involved in health and disease (jias57_20161101) (jias57_20161101)

Appears in the scientific report 2017

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Database coverage:
; ; Current Contents - Physical, Chemical and Earth Sciences ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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