德国弗莱堡大学Nils Wiedemann等研究人员合作揭示Tim17在线粒体前序蛋白转位中的核心作用。2023年8月1日，国际知名学术期刊《自然》在线发表了这一成果。

研究人员绘制了Tim17在原生膜环境中转运过程中与基质靶向和内膜分选前序蛋白的相互作用图。研究人员发现，Tim17在靠近双分子层膜间隙一侧含有保守的负电荷，这对于两类前体蛋白沿Tim17的独特跨膜腔启动前序蛋白转位至关重要。线粒体前序蛋白的两亲特性直接与这种依赖于Tim17的转运机制相匹配。这种机制允许内膜分选前体的跨膜片段直接横向释放到内膜中。

据悉，线粒体内膜前序转运酶（TIM23）是将核编码蛋白质导入线粒体的主要途径。在1000多种不同的线粒体蛋白质中，约有60%的蛋白质在合成时带有氨基末端的靶向信号（称为前序），前序形成带正电荷的两亲性α-螺旋。TIM23将前序蛋白分拣到内膜或基质中。关于必不可少的TIM23亚基Tim17的各种观点包括调控和耦合功能。

附：英文原文

Title: Central role of Tim17 in mitochondrial presequence protein translocation

Author: Fielden, Laura F., Busch, Jakob D., Merkt, Sandra G., Ganesan, Iniyan, Steiert, Conny, Hasselblatt, Hanna B., Busto, Jon V., Wirth, Christophe, Zufall, Nicole, Jungbluth, Sibylle, Noll, Katja, Dung, Julia M., Butenko, Ludmila, von der Malsburg, Karina, Koch, Hans-Georg, Hunte, Carola, van der Laan, Martin, Wiedemann, Nils

Issue&Volume: 2023-08-01

Abstract: The presequence translocase of the mitochondrial inner membrane (TIM23) represents the major route for the import of nuclear-encoded proteins into mitochondria1,2. About 60% of more than 1,000 different mitochondrial proteins are synthesised with amino-terminal targeting signals, termed presequences, which form positively charged amphiphilic α-helices3,4. TIM23 sorts the presequence proteins into the inner membrane or matrix. Various views including regulatory and coupling functions have been reported on the essential TIM23 subunit Tim175–7. We mapped the interaction of Tim17 with matrix-targeted and inner membrane-sorted preproteins during translocation in the native membrane environment. We show that Tim17 contains conserved negative charges close to the intermembrane space side of the bilayer, which are essential to initiate presequence protein translocation along a distinct transmembrane cavity of Tim17 for both classes of preproteins. The amphiphilic character of mitochondrial presequences directly matches this Tim17-dependent translocation mechanism. This mechanism permits direct lateral release of transmembrane segments of inner membrane-sorted precursors into the inner membrane.

DOI: 10.1038/s41586-023-06477-8

Source: https://www.nature.com/articles/s41586-023-06477-8