Hutu Dana P, Guiard Bernard, Chacinska Agnieszka, Becker Dorothea, Pfanner Nikolaus, Rehling Peter, van der Laan Martin
Institut für Biochemie und Molekularbiologie, ZBMZ, Germany.
Mol Biol Cell. 2008 Jun;19(6):2642-9. doi: 10.1091/mbc.e07-12-1226. Epub 2008 Apr 9.
The presequence translocase of the mitochondrial inner membrane (TIM23 complex) mediates the import of preproteins with amino-terminal presequences. To drive matrix translocation the TIM23 complex recruits the presequence translocase-associated motor (PAM) with the matrix heat shock protein 70 (mtHsp70) as central subunit. Activity and localization of mtHsp70 are regulated by four membrane-associated cochaperones: the adaptor protein Tim44, the stimulatory J-complex Pam18/Pam16, and Pam17. It has been proposed that Tim44 serves as molecular platform to localize mtHsp70 and the J-complex at the TIM23 complex, but it is unknown how Pam17 interacts with the translocase. We generated conditional tim44 yeast mutants and selected a mutant allele, which differentially affects the association of PAM modules with TIM23. In tim44-804 mitochondria, the interaction of the J-complex with the TIM23 complex is impaired, whereas unexpectedly the binding of Pam17 is increased. Pam17 interacts with the channel protein Tim23, revealing a new interaction site between TIM23 and PAM. Thus, the motor PAM is composed of functional modules that bind to different sites of the translocase. We suggest that Tim44 is not simply a scaffold for binding of motor subunits but plays a differential role in the recruitment of PAM modules to the inner membrane translocase.
线粒体内膜的前序列转位酶(TIM23复合物)介导具有氨基末端前序列的前体蛋白的导入。为了驱动基质转位,TIM23复合物募集前序列转位酶相关马达(PAM),其中基质热休克蛋白70(mtHsp70)作为核心亚基。mtHsp70的活性和定位由四种膜相关的共伴侣调节:衔接蛋白Tim44、刺激性J复合物Pam18/Pam16和Pam17。有人提出Tim44作为分子平台,将mtHsp70和J复合物定位在TIM23复合物上,但Pam17如何与转位酶相互作用尚不清楚。我们构建了条件性tim44酵母突变体,并选择了一个突变等位基因,该等位基因差异地影响PAM模块与TIM23的结合。在tim44-804线粒体中,J复合物与TIM23复合物的相互作用受损,而出乎意料的是,Pam17的结合增加。Pam17与通道蛋白Tim23相互作用,揭示了TIM23与PAM之间的一个新的相互作用位点。因此,马达PAM由结合到转位酶不同位点的功能模块组成。我们认为Tim44不仅仅是一个用于结合马达亚基的支架,而是在将PAM模块募集到内膜转位酶中发挥不同的作用。