Crystal structures of the NO sensor NsrR reveal how its iron-sulfur cluster modulates DNA binding

Anne Volbeda; Erin L. Dodd; Claudine Darnault; Jason C. Crack; Oriane Renoux; Matthew I. Hutchings; Nick E. Le Brun; Juan C. Fontecilla-Camps

doi:10.1038/ncomms15052

Crystal structures of the NO sensor NsrR reveal how its iron-sulfur cluster modulates DNA binding

Anne Volbeda, Erin L. Dodd, Claudine Darnault, Jason C. Crack, Oriane Renoux, Matthew I. Hutchings, Nick E. Le Brun, Juan C. Fontecilla-Camps

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Abstract

NsrR from Streptomyces coelicolor (Sc) regulates the expression of three genes through the progressive degradation of its [4Fe–4S] cluster on nitric oxide (NO) exposure. We report the 1.95 Å resolution crystal structure of dimeric holo-ScNsrR and show that the cluster is coordinated by the three invariant Cys residues from one monomer and, unexpectedly, Asp8 from the other. A cavity map suggests that NO displaces Asp8 as a cluster ligand and, while D8A and D8C variants remain NO sensitive, DNA binding is affected. A structural comparison of holo-ScNsrR with an apo-IscR-DNA complex shows that the [4Fe–4S] cluster stabilizes a turn between ScNsrR Cys93 and Cys99 properly oriented to interact with the DNA backbone. In addition, an apo ScNsrR structure suggests that Asn97 from this turn, along with Arg12, which forms a salt-bridge with Asp8, are instrumental in modulating the position of the DNA recognition helix region relative to its major groove.

Original language	English
Article number	15052
Journal	Nature Communications
Volume	8
DOIs	https://doi.org/10.1038/ncomms15052
Publication status	Published - 20 Apr 2017

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Nick Le Brun
- N.Le-brunuea.acuk
- School of Chemistry, Pharmacy and Pharmacology - Professor of Biological Chemistry
- Centre for Molecular and Structural Biochemistry - Director
- Chemistry of Life Processes - Member
Person: Research Group Member, Academic, Teaching & Research

Biological roles and mechanisms of nitric oxide reactions with iron-sulfur cluster transcriptional regulators
Le Brun, N., Hutchings, M., Thomson, A. & Cull, N.
Biotechnology and Biological Sciences Research Council
1/07/12 → 30/06/15
Project: Research

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title = "Crystal structures of the NO sensor NsrR reveal how its iron-sulfur cluster modulates DNA binding",

abstract = "NsrR from Streptomyces coelicolor (Sc) regulates the expression of three genes through the progressive degradation of its [4Fe–4S] cluster on nitric oxide (NO) exposure. We report the 1.95 {\AA} resolution crystal structure of dimeric holo-ScNsrR and show that the cluster is coordinated by the three invariant Cys residues from one monomer and, unexpectedly, Asp8 from the other. A cavity map suggests that NO displaces Asp8 as a cluster ligand and, while D8A and D8C variants remain NO sensitive, DNA binding is affected. A structural comparison of holo-ScNsrR with an apo-IscR-DNA complex shows that the [4Fe–4S] cluster stabilizes a turn between ScNsrR Cys93 and Cys99 properly oriented to interact with the DNA backbone. In addition, an apo ScNsrR structure suggests that Asn97 from this turn, along with Arg12, which forms a salt-bridge with Asp8, are instrumental in modulating the position of the DNA recognition helix region relative to its major groove.",

author = "Anne Volbeda and Dodd, {Erin L.} and Claudine Darnault and Crack, {Jason C.} and Oriane Renoux and Hutchings, {Matthew I.} and {Le Brun}, {Nick E.} and Fontecilla-Camps, {Juan C.}",

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T1 - Crystal structures of the NO sensor NsrR reveal how its iron-sulfur cluster modulates DNA binding

AU - Volbeda, Anne

AU - Dodd, Erin L.

AU - Darnault, Claudine

AU - Crack, Jason C.

AU - Renoux, Oriane

AU - Hutchings, Matthew I.

AU - Le Brun, Nick E.

AU - Fontecilla-Camps, Juan C.

PY - 2017/4/20

Y1 - 2017/4/20

N2 - NsrR from Streptomyces coelicolor (Sc) regulates the expression of three genes through the progressive degradation of its [4Fe–4S] cluster on nitric oxide (NO) exposure. We report the 1.95 Å resolution crystal structure of dimeric holo-ScNsrR and show that the cluster is coordinated by the three invariant Cys residues from one monomer and, unexpectedly, Asp8 from the other. A cavity map suggests that NO displaces Asp8 as a cluster ligand and, while D8A and D8C variants remain NO sensitive, DNA binding is affected. A structural comparison of holo-ScNsrR with an apo-IscR-DNA complex shows that the [4Fe–4S] cluster stabilizes a turn between ScNsrR Cys93 and Cys99 properly oriented to interact with the DNA backbone. In addition, an apo ScNsrR structure suggests that Asn97 from this turn, along with Arg12, which forms a salt-bridge with Asp8, are instrumental in modulating the position of the DNA recognition helix region relative to its major groove.

AB - NsrR from Streptomyces coelicolor (Sc) regulates the expression of three genes through the progressive degradation of its [4Fe–4S] cluster on nitric oxide (NO) exposure. We report the 1.95 Å resolution crystal structure of dimeric holo-ScNsrR and show that the cluster is coordinated by the three invariant Cys residues from one monomer and, unexpectedly, Asp8 from the other. A cavity map suggests that NO displaces Asp8 as a cluster ligand and, while D8A and D8C variants remain NO sensitive, DNA binding is affected. A structural comparison of holo-ScNsrR with an apo-IscR-DNA complex shows that the [4Fe–4S] cluster stabilizes a turn between ScNsrR Cys93 and Cys99 properly oriented to interact with the DNA backbone. In addition, an apo ScNsrR structure suggests that Asn97 from this turn, along with Arg12, which forms a salt-bridge with Asp8, are instrumental in modulating the position of the DNA recognition helix region relative to its major groove.

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DO - 10.1038/ncomms15052

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SN - 2041-1723

VL - 8

JO - Nature Communications

JF - Nature Communications

M1 - 15052

ER -

Crystal structures of the NO sensor NsrR reveal how its iron-sulfur cluster modulates DNA binding

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Nick Le Brun

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Biological roles and mechanisms of nitric oxide reactions with iron-sulfur cluster transcriptional regulators

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