Anatomy of an iron-sulfur cluster scaffold protein: Understanding the determinants of [2Fe-2S] cluster stability on IscU
Anatomy of an iron-sulfur cluster scaffold protein: Understanding the determinants of [2Fe-2S] cluster stability on IscU
复制标题
DOI：
10.1016/j.bbamcr.2014.10.023
复制
发表时间：
2015-06-01
影响因子：
5.1
通讯作者：
Pastore, Annalisa
中科院分区：
文献类型：
--
作者：
Adrover, Miguel;Howes, Barry D.;Pastore, Annalisa
蛋白质结合的铁硫簇是参与多种代谢途径的辅基。因此，了解它们如何与宿主蛋白相互作用以及哪些因素影响它们的稳定性是生物学的一个重要目标。在这里，我们已经解决了这个问题，通过研究的决定因素的2Fe-2S簇的稳定性在IscU/Isu蛋白质支架。通过一个详细的计算研究的基础上的混合量子和经典力学的方法，我们预测，同时存在的两个保守的残基，D39和H105，有一个冲突的作用，在集群协调，导致不稳定的集群负载IscU/Isu根据“拔河”机制。该效应在已知更稳定地宿主簇的D39 A突变体中不存在。我们的理论结论直接得到实验数据的支持，也从H105 A突变体，它具有野生型和D39 A突变体之间的中间属性。本文是特刊的一部分，题为：Fe/S蛋白质：分析，结构，功能，生物起源和疾病。(C)2014爱思唯尔有限公司版权所有。
Protein-bound iron sulfur clusters are prosthetic groups involved in several metabolic pathways. Understanding how they interact with the host protein and which factors influence their stability is therefore an important goal in biology. Here, we have addressed this question by studying the determinants of the 2Fe-2S cluster stability in the IscU/Isu protein scaffold. Through a detailed computational study based on a mixed quantum and classical mechanics approach, we predict that the simultaneous presence of two conserved residues, D39 and H105, has a conflicting role in cluster coordination which results in destabilizing cluster-loaded IscU/Isu according to a 'tug-of-war' mechanism. The effect is absent in the D39A mutant already known to host the cluster more stably. Our theoretical conclusions are directly supported by experimental data, also obtained from the H105A mutant, which has properties intermediate between the wild-type and the D39A mutant. This article is part of a Special Issue entitled: Fe/S proteins: Analysis, structure, function, biogenesis and diseases. (C) 2014 Elsevier B.V. All rights reserved.