Genetic and structural characterization of the human mitochondrial inner membrane translocase
Genetic and structural characterization of the human mitochondrial inner membrane translocase
复制标题
DOI：
10.1006/jmbi.1999.2751
复制
发表时间：
1999-05-28
影响因子：
5.6
通讯作者：
Hofmann, S
中科院分区：
文献类型：
--
作者：
Bauer, MF;Gempel, K;Hofmann, S
核编码的线粒体前蛋白的易位由外膜和内膜中的易位酶介导。在酵母酿酒酵母中，前蛋白转运到基质中需要膜蛋白Tim 23、Tim 17和Tim 44，它们与mtHsp 70及其共伴侣Mge 1 p合作驱动转运。我们克隆并功能分析了Tim 17，Tim 23和Tim 44的人类同源物。与酵母相反，发现两个TIM 17基因在人类中表达。TIM 44、TIM 23和TIM 17 a基因定位于染色体19p13.2-p13.3、10q11.21-q11.23和1 q32。TIM 17 b基因定位于Xp11.23，在融合点附近，一个常染色体区域被认为是在大约80-130 MY前被添加到X染色体的“古老”部分。两种蛋白质hTim 17 a和hTim 17 b的一级序列基本相同，显著差异仅限于它们的C末端。它们在胎儿和成人组织中普遍表达，并且都显示出与hTim 23相当的表达水平。人Tim组分的生化表征显示，hTim 44位于基质中，与酵母相反，仅与内膜松散相关。hTim 23在内膜中被组织成两个不同的复合物，一个含有hTim 17 a，一个含有hTim 17 b。两种TIM复合物均显示出110 kDa的天然分子量。我们认为，TIM 23的结构组织。17个前蛋白转位酶从低等真核生物到高等真核生物都是保守的。(C)北京：科学出版社.
Translocation of nuclear-encoded mitochondrial preproteins is mediated by translocases in the outer and inner membranes. In the yeast Saccharomyces cerevisiae, translocation of preproteins into the matrix requires the membrane proteins Tim23, Tim17 and Tim44, which drive translocation in cooperation with mtHsp70 and its co-chaperone Mge1p. We have cloned and functionally analyzed the human homologues of Tim17, Tim23 and Tim44. In contrast to yeast, two TIM17 genes were found to be expressed in humans. TIM44, TIM23 and TIM17a genes were mapped to chromosomes 19p13.2-p13.3, 10q11.21-q11.23 and 1q32. The TIM17b gene mapped to Xp11.23, near the fusion point where an autosomal region was proposed to have been added to the "ancient" part of the X chromosome about 80-130 MY ago. The primary sequences of the two proteins, hTim17a and hTim17b, are essentially identical, significant differences being restricted to their C termini. They are ubiquitously expressed in fetal and adult tissues, and both show expression levels comparable to that of hTim23. Biochemical characterization of the human Tim components revealed that hTim44 is localized in the matrix and, in contrast to yeast, only loosely associated with the inner membrane. hTim23 is organized into two distinct complexes in the inner membrane, one containing hTim17a and one containing hTim17b. Both TIM complexes display a native molecular mass of 110 kDa. We suggest that the structural organization of TIM23 . 17 preprotein translocases is conserved from low to high eukaryotes. (C) 1999 Academic Press.