Biocenter-Department of Cell Biology, LMU Munich, Munich, Germany.
Department of Parasitology, Faculty of Science, Charles University, BIOCEV, Vestec, Czech Republic.
Life Sci Alliance. 2023 Sep 25;6(12). doi: 10.26508/lsa.202302122. Print 2023 Dec.
Hundreds of mitochondrial proteins with N-terminal presequences are translocated across the outer and inner mitochondrial membranes via the TOM and TIM23 complexes, respectively. How translocation of proteins across two mitochondrial membranes is coordinated is largely unknown. Here, we show that the two domains of Tim50 in the intermembrane space, named core and PBD, both have essential roles in this process. Building upon the surprising observation that the two domains of Tim50 can complement each other , we establish that the core domain contains the main presequence-binding site and serves as the main recruitment point to the TIM23 complex. On the other hand, the PBD plays, directly or indirectly, a critical role in cooperation of the TOM and TIM23 complexes and supports the receptor function of Tim50. Thus, the two domains of Tim50 both have essential but distinct roles and together coordinate translocation of proteins across two mitochondrial membranes.
数百种带有 N 端前导序列的线粒体蛋白分别通过 TOM 和 TIM23 复合物穿过外膜和内膜。然而，蛋白质如何协调穿过两层线粒体膜的易位在很大程度上是未知的。在这里，我们表明，位于膜间空间的 Tim50 的两个结构域，称为核心和 PBD，在这个过程中都起着重要作用。基于 Tim50 的两个结构域可以相互补充的惊人观察结果，我们确定核心结构域包含主要的前导序列结合位点，并作为主要募集点到 TIM23 复合物。另一方面，PBD 直接或间接地在 TOM 和 TIM23 复合物的合作中发挥关键作用，并支持 Tim50 的受体功能。因此，Tim50 的两个结构域都具有重要但不同的作用，并共同协调蛋白质穿过两层线粒体膜的易位。
