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Understanding the role of dynamics in the iron sulfur cluster molecular machine

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Understanding the role of dynamics in the iron sulfur cluster molecular machine. / di Maio, Danilo; Chandramouli, Balasubramanian; Yan, Robert; Brancato, Giuseppe; Pastore, Annalisa.

In: BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 26.07.2016.

Research output: Contribution to journalArticle

Harvard

di Maio, D, Chandramouli, B, Yan, R, Brancato, G & Pastore, A 2016, 'Understanding the role of dynamics in the iron sulfur cluster molecular machine', BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS. https://doi.org/10.1016/j.bbagen.2016.07.020

APA

di Maio, D., Chandramouli, B., Yan, R., Brancato, G., & Pastore, A. (2016). Understanding the role of dynamics in the iron sulfur cluster molecular machine. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS. https://doi.org/10.1016/j.bbagen.2016.07.020

Vancouver

di Maio D, Chandramouli B, Yan R, Brancato G, Pastore A. Understanding the role of dynamics in the iron sulfur cluster molecular machine. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS. 2016 Jul 26. https://doi.org/10.1016/j.bbagen.2016.07.020

Author

di Maio, Danilo ; Chandramouli, Balasubramanian ; Yan, Robert ; Brancato, Giuseppe ; Pastore, Annalisa. / Understanding the role of dynamics in the iron sulfur cluster molecular machine. In: BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS. 2016.

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@article{5c97a36155444edcb578f3113594ffeb,
title = "Understanding the role of dynamics in the iron sulfur cluster molecular machine",
abstract = "BackgroundThe bacterial proteins IscS, IscU and CyaY, the bacterial orthologue of frataxin, play an essential role in the biological machine that assembles the prosthetic Fe-S cluster groups on proteins. They form functionally binary and ternary complexes both in vivo and in vitro. Yet, the mechanism by which they work remains unclear.MethodsWe carried out extensive molecular dynamics simulations to understand the nature of their interactions and the role of dynamics starting from the crystal structure of a IscS-IscU complex and the experimentally-based model of a ternary IscS-IscU-CyaY complex and used nuclear magnetic resonance to experimentally test the interface.ResultsWe show that, while being firmly anchored to IscS, IscU has a pivotal motion around the interface. Our results also describe how the catalytic loop of IscS can flip conformation to allow Fe-S cluster assembly. This motion is hampered in the ternary complex explaining its inhibitory properties in cluster formation.ConclusionsWe conclude that the observed ‘fluid’ IscS-IscU interface provides the binary complex with a functional adaptability exploited in partner recognition and unravels the molecular determinants of the reported inhibitory action of CyaY in the IscS-IscU-CyaY complex explained in terms of the hampering effect on specific IscU-IscS movements.General significanceOur study provides the first mechanistic basis to explain how the IscS-IscU complex selects their binding partners and supports the inhibitory role of CyaY in the ternary complex.",
keywords = "CyaY, Frataxin, Iron-sulfur cluster biogenesis, Molecular dynamics, Structure",
author = "{di Maio}, Danilo and Balasubramanian Chandramouli and Robert Yan and Giuseppe Brancato and Annalisa Pastore",
year = "2016",
month = "7",
day = "26",
doi = "10.1016/j.bbagen.2016.07.020",
language = "English",
journal = "BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS",
issn = "0304-4165",
publisher = "Elsevier",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Understanding the role of dynamics in the iron sulfur cluster molecular machine

AU - di Maio, Danilo

AU - Chandramouli, Balasubramanian

AU - Yan, Robert

AU - Brancato, Giuseppe

AU - Pastore, Annalisa

PY - 2016/7/26

Y1 - 2016/7/26

N2 - BackgroundThe bacterial proteins IscS, IscU and CyaY, the bacterial orthologue of frataxin, play an essential role in the biological machine that assembles the prosthetic Fe-S cluster groups on proteins. They form functionally binary and ternary complexes both in vivo and in vitro. Yet, the mechanism by which they work remains unclear.MethodsWe carried out extensive molecular dynamics simulations to understand the nature of their interactions and the role of dynamics starting from the crystal structure of a IscS-IscU complex and the experimentally-based model of a ternary IscS-IscU-CyaY complex and used nuclear magnetic resonance to experimentally test the interface.ResultsWe show that, while being firmly anchored to IscS, IscU has a pivotal motion around the interface. Our results also describe how the catalytic loop of IscS can flip conformation to allow Fe-S cluster assembly. This motion is hampered in the ternary complex explaining its inhibitory properties in cluster formation.ConclusionsWe conclude that the observed ‘fluid’ IscS-IscU interface provides the binary complex with a functional adaptability exploited in partner recognition and unravels the molecular determinants of the reported inhibitory action of CyaY in the IscS-IscU-CyaY complex explained in terms of the hampering effect on specific IscU-IscS movements.General significanceOur study provides the first mechanistic basis to explain how the IscS-IscU complex selects their binding partners and supports the inhibitory role of CyaY in the ternary complex.

AB - BackgroundThe bacterial proteins IscS, IscU and CyaY, the bacterial orthologue of frataxin, play an essential role in the biological machine that assembles the prosthetic Fe-S cluster groups on proteins. They form functionally binary and ternary complexes both in vivo and in vitro. Yet, the mechanism by which they work remains unclear.MethodsWe carried out extensive molecular dynamics simulations to understand the nature of their interactions and the role of dynamics starting from the crystal structure of a IscS-IscU complex and the experimentally-based model of a ternary IscS-IscU-CyaY complex and used nuclear magnetic resonance to experimentally test the interface.ResultsWe show that, while being firmly anchored to IscS, IscU has a pivotal motion around the interface. Our results also describe how the catalytic loop of IscS can flip conformation to allow Fe-S cluster assembly. This motion is hampered in the ternary complex explaining its inhibitory properties in cluster formation.ConclusionsWe conclude that the observed ‘fluid’ IscS-IscU interface provides the binary complex with a functional adaptability exploited in partner recognition and unravels the molecular determinants of the reported inhibitory action of CyaY in the IscS-IscU-CyaY complex explained in terms of the hampering effect on specific IscU-IscS movements.General significanceOur study provides the first mechanistic basis to explain how the IscS-IscU complex selects their binding partners and supports the inhibitory role of CyaY in the ternary complex.

KW - CyaY

KW - Frataxin

KW - Iron-sulfur cluster biogenesis

KW - Molecular dynamics

KW - Structure

U2 - 10.1016/j.bbagen.2016.07.020

DO - 10.1016/j.bbagen.2016.07.020

M3 - Article

JO - BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS

JF - BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS

SN - 0304-4165

ER -

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