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

doi:10.1021/acs.jpcb.7b10584

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

Department of Plant and Environmental Sciences (Natural Sciences)

Research output: Contribution to journal › Article › peer-review

16 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 language	American English
Pages (from-to)	10648-10656
Number of pages	9
Journal	Journal of Physical Chemistry B
Volume	121
Issue number	47
DOIs	https://doi.org/10.1021/acs.jpcb.7b10584
State	Published - 30 Nov 2017

Bibliographical note

Funding Information:
R.N., R.M., and P.A.J. acknowledge the support of NSF-MCB-1613462 (R.M.), BSF Grant 2015831 (R.N.), and NIH Grant GM101467 (P.A.J.). We acknowledge the computing time granted by JARA-HPC and very fruitful discussions with Prof. Maria Ramos.

Publisher Copyright:
© 2017 American Chemical Society.

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Pesce, L., Calandrini, V., Marjault, H. B., Lipper, C. H., Rossetti, G., Mittler, R., Jennings, P. A., Bauer, A., Nechushtai, R., & Carloni, P. (2017). Molecular Dynamics Simulations of the [2Fe-2S] Cluster-Binding Domain of NEET Proteins Reveal Key Molecular Determinants That Induce Their Cluster Transfer/Release. Journal of Physical Chemistry B, 121(47), 10648-10656. https://doi.org/10.1021/acs.jpcb.7b10584

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

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.",

author = "Luca Pesce and Vania Calandrini and Marjault, {Henri Baptiste} and Lipper, {Colin H.} and Gulia Rossetti and Ron Mittler and Jennings, {Patricia A.} and Andreas Bauer and Rachel Nechushtai and Paolo Carloni",

note = "Funding Information: R.N., R.M., and P.A.J. acknowledge the support of NSF-MCB-1613462 (R.M.), BSF Grant 2015831 (R.N.), and NIH Grant GM101467 (P.A.J.). We acknowledge the computing time granted by JARA-HPC and very fruitful discussions with Prof. Maria Ramos. Publisher Copyright: {\textcopyright} 2017 American Chemical Society.",

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doi = "10.1021/acs.jpcb.7b10584",

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Pesce, L, Calandrini, V, Marjault, HB, Lipper, CH, Rossetti, G, Mittler, R, Jennings, PA, Bauer, A, Nechushtai, R & Carloni, P 2017, 'Molecular Dynamics Simulations of the [2Fe-2S] Cluster-Binding Domain of NEET Proteins Reveal Key Molecular Determinants That Induce Their Cluster Transfer/Release', Journal of Physical Chemistry B, vol. 121, no. 47, pp. 10648-10656. https://doi.org/10.1021/acs.jpcb.7b10584

Molecular Dynamics Simulations of the [2Fe-2S] Cluster-Binding Domain of NEET Proteins Reveal Key Molecular Determinants That Induce Their Cluster Transfer/Release. / Pesce, Luca; Calandrini, Vania; Marjault, Henri Baptiste et al.
In: Journal of Physical Chemistry B, Vol. 121, No. 47, 30.11.2017, p. 10648-10656.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Molecular Dynamics Simulations of the [2Fe-2S] Cluster-Binding Domain of NEET Proteins Reveal Key Molecular Determinants That Induce Their Cluster Transfer/Release

AU - Pesce, Luca

AU - Calandrini, Vania

AU - Marjault, Henri Baptiste

AU - Lipper, Colin H.

AU - Rossetti, Gulia

AU - Mittler, Ron

AU - Jennings, Patricia A.

AU - Bauer, Andreas

AU - Nechushtai, Rachel

AU - Carloni, Paolo

N1 - Funding Information: R.N., R.M., and P.A.J. acknowledge the support of NSF-MCB-1613462 (R.M.), BSF Grant 2015831 (R.N.), and NIH Grant GM101467 (P.A.J.). We acknowledge the computing time granted by JARA-HPC and very fruitful discussions with Prof. Maria Ramos. Publisher Copyright: © 2017 American Chemical Society.

PY - 2017/11/30

Y1 - 2017/11/30

N2 - 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.

AB - 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.

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DO - 10.1021/acs.jpcb.7b10584

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AN - SCOPUS:85036625559

SN - 1520-6106

VL - 121

SP - 10648

EP - 10656

JO - Journal of Physical Chemistry B

JF - Journal of Physical Chemistry B

IS - 47

ER -

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

Abstract

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