Molecular Dynamics Simulations of the [2Fe-2S] Cluster-Binding Domain of NEET Proteins Reveal Key Molecular Determinants That Induce Their Cluster Transfer/Release

Luca Pesce, Vania Calandrini, Henri Baptiste Marjault, Colin H. Lipper, Gulia Rossetti, Ron Mittler, Patricia A. Jennings, Andreas Bauer, Rachel Nechushtai*, Paolo Carloni

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

The NEET proteins are a novel family of iron-sulfur proteins characterized by an unusual three cysteine and one histidine coordinated [2Fe-2S] cluster. Aberrant cluster release, facilitated by the breakage of the Fe-N bond, is implicated in a variety of human diseases, including cancer. Here, the molecular dynamics in the multi-microsecond 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 in 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 the pH-dependent cluster reactivity. The reliability of our conclusions is established by an extensive comparison with the NMR data of the solution proteins, in part measured in this work.

Original languageAmerican English
Pages (from-to)10648-10656
Number of pages9
JournalJournal of Physical Chemistry B
Volume121
Issue number47
DOIs
StatePublished - 30 Nov 2017

Bibliographical note

Publisher Copyright:
© 2017 American Chemical Society.

Fingerprint

Dive into the research topics of 'Molecular Dynamics Simulations of the [2Fe-2S] Cluster-Binding Domain of NEET Proteins Reveal Key Molecular Determinants That Induce Their Cluster Transfer/Release'. Together they form a unique fingerprint.

Cite this