Domain Organization of the Monomeric Form of the Tom70 Mitochondrial Import Receptor
Domain Organization of the Monomeric Form of the Tom70 Mitochondrial Import Receptor
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DOI：
10.1016/j.jmb.2009.03.070
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发表时间：
2009-05-22
影响因子：
5.6
通讯作者：
Mulhern, Terrence D.
中科院分区：
文献类型：
--
作者：
Mills, Ryan D.;Trewhella, Jill;Mulhern, Terrence D.
Tom 70是一种线粒体蛋白输入受体，由11个三角肽重复序列（TPR）组成。前三个TPR形成一个N-末端结构域，其招募热休克蛋白家族伴侣，而八个C-末端TPR形成一个结构域，其从结合的伴侣接收注定要输入的线粒体前体蛋白。分析超离心和溶液小角X射线散射（SAXS）分析的特征在于Tom 70作为一个细长的单体。基于对Tom 70二聚体晶体结构中观察到的结构域配对的替代解释，提出了Tom 70单体的模型，并对SAXS数据进行了改进。在Tom 70单体的这种“开放”模型中，分子伴侣和生物标记物结合位点暴露并并排位于分子的一面。荧光各向异性测量表明，单体Tom 70可以结合分子伴侣和前体肽，分子伴侣肽结合不改变Tom 70的前体肽的亲和力。SAXS不能检测到伴侣结合后Tom 70的任何形状变化。然而，分子模拟表明，伴侣结合与Tom 70二聚体的形成是不相容的。推测Tom 70单体是介导初始分子伴侣对接和前体识别的功能单元。(C)2009爱思唯尔有限公司保留所有权利。
Tom70 is a mitochondrial protein import receptor composed of 11 tetratricopeptide repeats (TPRs). The first three TPRs form an N-terminal domain that recruits heat shock protein family chaperones, while the eight C-terminal TPRs form a domain that receives, from the bound chaperone, mitochondrial precursor proteins destined for import. Analytical Ultracentrifugation and solution small-angle X-ray scattering (SAXS) analysis characterized Tom70 as an elongated monomer. A model for the Tom70 monomer was proposed based on the alternate interpretation of the domain pairings observed in the crystal structure of the Tom70 dimer and refined against the SAXS data. In this "open" model of the Tom70 monomer, the chaperone- and precursor-binding sites are exposed and lay side by side oil one face of the molecule. Fluorescence anisotropy measurements indicated that monomeric Tom70 can bind both chaperone and precursor peptides and that chaperone peptide binding does not alter the affinity of Tom70 for the precursor peptide. SAXS Was unable to detect any shape change in Tom70 upon chaperone binding. However, molecular modeling indicated that chaperone binding is incompatible with Tom70 dimer formation. It is proposed that the Tom70 monomer is the functional unit mediating initial chaperone docking and precursor recognition. (C) 2009 Elsevier Ltd. All rights reserved.