与铁蛋白IRE-RNA复合的双功能铁调节蛋白1的结构

Structure of dual function iron regulatory protein 1 complexed with ferritin IRE-RNA.

作者信息

Walden William E, Selezneva Anna I, Dupuy Jérôme, Volbeda Anne, Fontecilla-Camps Juan C, Theil Elizabeth C, Volz Karl

机构信息

Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL 60612-7344, USA.

出版信息

Science. 2006 Dec 22;314(5807):1903-8. doi: 10.1126/science.1133116.

DOI:10.1126/science.1133116

PMID:17185597

Abstract

Iron regulatory protein 1 (IRP1) binds iron-responsive elements (IREs) in messenger RNAs (mRNAs), to repress translation or degradation, or binds an iron-sulfur cluster, to become a cytosolic aconitase enzyme. The 2.8 angstrom resolution crystal structure of the IRP1:ferritin H IRE complex shows an open protein conformation compared with that of cytosolic aconitase. The extended, L-shaped IRP1 molecule embraces the IRE stem-loop through interactions at two sites separated by approximately 30 angstroms, each involving about a dozen protein:RNA bonds. Extensive conformational changes related to binding the IRE or an iron-sulfur cluster explain the alternate functions of IRP1 as an mRNA regulator or enzyme.

摘要

铁调节蛋白1（IRP1）与信使核糖核酸（mRNA）中的铁反应元件（IRE）结合，以抑制翻译或降解，或者与铁硫簇结合，成为一种胞质乌头酸酶。与胞质乌头酸酶相比，IRP1：铁蛋白H IRE复合物2.8埃分辨率的晶体结构显示出一种开放的蛋白质构象。延伸的L形IRP1分子通过在相隔约30埃的两个位点的相互作用包围IRE茎环，每个位点涉及约一打蛋白质：RNA键。与结合IRE或铁硫簇相关的广泛构象变化解释了IRP1作为mRNA调节剂或酶的交替功能。