State Key Laboratory of Membrane Biology, Peking-Tsinghua Center for Life Sciences, School of Life Sciences, Peking University, Beijing 100871, China.
Center for Quantitative Biology, Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
Proc Natl Acad Sci U S A. 2023 Jan 10;120(2):e2208070120. doi: 10.1073/pnas.2208070120. Epub 2023 Jan 4.
Secretory proteins are cotranslationally or posttranslationally translocated across lipid membranes via a protein-conducting channel named SecY in prokaryotes and Sec61 in eukaryotes. The vast majority of secretory proteins in bacteria are driven through the channel posttranslationally by SecA, a highly conserved ATPase. How a polypeptide chain is moved by SecA through the SecY channel is poorly understood. Here, we report electron cryomicroscopy structures of the active SecA-SecY translocon with a polypeptide substrate. The substrate is captured in different translocation states when clamped by SecA with different nucleotides. Upon binding of an ATP analog, SecA undergoes global conformational changes to push the polypeptide substrate toward the channel in a way similar to how the RecA-like helicases translocate their nucleic acid substrates. The movements of the polypeptide substrates in the SecA-SecY translocon share a similar structural basis to those in the ribosome-SecY complex during cotranslational translocation.
分泌蛋白通过一种称为 SecY 的蛋白导通道，在原核生物中转位或翻译后转位穿过脂膜，在真核生物中称为 Sec61。大多数细菌的分泌蛋白在 SecA 的驱动下通过通道进行翻译后转运，SecA 是一种高度保守的 ATP 酶。SecA 如何通过 SecY 通道移动多肽链尚不清楚。在这里，我们报告了带有多肽底物的活性 SecA-SecY 转运蛋白的电子 cryomicroscopy 结构。当用不同的核苷酸夹住 SecA 时，底物被捕获在不同的转运状态下。在结合 ATP 类似物后，SecA 会发生全局构象变化，以类似于 RecA 样解旋酶转运其核酸底物的方式将多肽底物推向通道。多肽底物在 SecA-SecY 转运蛋白中的运动与核糖体-SecY 复合物在共翻译转运过程中的运动具有相似的结构基础。
