Rojo E E, Guiard B, Neupert W, Stuart R A
Institut für Physiologische Chemie, Geethestrasse 33, 80336 München, Germany.
J Biol Chem. 1998 Apr 3;273(14):8040-7. doi: 10.1074/jbc.273.14.8040.
D-Lactate dehydrogenase (D-LD) is located in the inner membrane of mitochondria. It spans the membrane once in an Nin-Cout orientation with the bulk of the protein residing as a folded domain in the intermembrane space. D-LD is synthesized as a precursor with an N-terminal cleavable presequence and is imported into the mitochondria in a Deltapsi-dependent, but mt-Hsp70-independent manner. Upon import in vitro D-LD folds in the intermembrane space to attain a conformation indistinguishable from endogenous D-LD. Sorting of D-LD to the inner membrane is directed by a composite topogenic signal consisting of the hydrophobic transmembrane segment and a cluster of charged amino acids C-terminal to it. We propose a model for the mode of operation of the sorting signal of D-LD. This model also accounts for the driving force of translocation across the outer membrane, in the apparent absence of mt-Hsp70-dependent assisted import and involves the folding of the D-LD in the intermembrane space.
D-乳酸脱氢酶（D-LD）位于线粒体内膜。它以Nin-Cout方向跨膜一次，大部分蛋白质以折叠结构域的形式存在于膜间隙中。D-LD作为一种具有N端可裂解前序列的前体被合成，并以依赖于Δψ但不依赖于线粒体热休克蛋白70（mt-Hsp70）的方式导入线粒体。在体外导入时，D-LD在膜间隙中折叠，以获得与内源性D-LD无法区分的构象。D-LD向内膜的分选由一个复合拓扑信号引导，该信号由疏水跨膜片段及其C端的一组带电荷氨基酸组成。我们提出了一个D-LD分选信号作用模式的模型。该模型还解释了在明显缺乏mt-Hsp70依赖的辅助导入的情况下，跨外膜转运的驱动力，并且涉及D-LD在膜间隙中的折叠。
