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

Research output: Contribution to journalArticle

Danilo di Maio, Balasubramanian Chandramouli, Robert Yan, Giuseppe Brancato, Annalisa Pastore

Original languageEnglish
JournalBIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
Early online date26 Jul 2016
DOIs
Publication statusE-pub ahead of print - 26 Jul 2016

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Abstract

Background

The 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.
Methods

We 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.
Results

We 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.
Conclusions

We 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 significance

Our 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.

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