Melin Jonathan, Kilisch Markus, Neumann Piotr, Lytovchenko Oleksandr, Gomkale Ridhima, Schendzielorz Alexander, Schmidt Bernhard, Liepold Thomas, Ficner Ralf, Jahn Olaf, Rehling Peter, Schulz Christian
Institute of Cellular Biochemistry, University Medical Center Göttingen, Germany.
Department of Molecular Biology, University Medical Center Göttingen, Germany.
Biochim Biophys Acta. 2015 Aug;1853(8):1850-9. doi: 10.1016/j.bbamcr.2015.04.021. Epub 2015 May 7.
The translocase of the outer mitochondrial membrane (TOM complex) is the general entry gate into mitochondria for almost all imported proteins. A variety of specific receptors allow the TOM complex to recognize targeting signals of various precursor proteins that are transported along different import pathways. Aside from the well-characterized presequence receptors Tom20 and Tom22 a third TOM receptor, Tom70, binds proteins of the carrier family containing multiple transmembrane segments. Here we demonstrate that Tom70 directly binds to presequence peptides using a dedicated groove. A single point mutation in the cavity of this pocket (M551R) reduces the presequence binding affinity of Tom70 ten-fold and selectively impairs import of the presequence-containing precursor Mdl1 but not the ADP/ATP carrier (AAC). Hence Tom70 contributes to the presequence import pathway by recognition of the targeting signal of the Mdl1 precursor.
线粒体外膜转位酶（TOM复合体）几乎是所有导入蛋白进入线粒体的通用入口。多种特异性受体使TOM复合体能够识别沿不同导入途径运输的各种前体蛋白的靶向信号。除了已充分表征的前序列受体Tom20和Tom22外，第三个TOM受体Tom70可结合含有多个跨膜片段的载体家族蛋白。在这里，我们证明Tom70利用一个专用凹槽直接结合前序列肽。该口袋腔内的一个单点突变（M551R）使Tom70的前序列结合亲和力降低了十倍，并选择性地损害了含前序列的前体Mdl1的导入，但不影响ADP/ATP载体（AAC）的导入。因此，Tom70通过识别Mdl1前体的靶向信号，促进了前序列导入途径。
