小柯机器人

美国纽约大学医学院Damian C. Ekiert等研究人员合作揭示内源性分枝杆菌MCE脂质转运体的结构。2023年7月26日，《自然》杂志在线发表了这项成果。

研究人员表示，为了在巨噬细胞内复制并导致结核病，结核分枝杆菌必须从宿主体内清除各种营养物质。哺乳动物细胞进入（MCE）蛋白是结核分枝杆菌的重要毒力因子，它们由大型基因簇编码，与脂肪酸和胆固醇穿过不透水的分枝杆菌细胞包膜的运输有关。人们对货物如何通过这一屏障运输知之甚少，目前仍不清楚分枝杆菌mce基因簇编码的约十种蛋白质是如何组装以运输货物通过细胞包膜的。

研究人员报告了烟草分枝杆菌（Mycobacterium smegmatis，结核分枝杆菌的非致病亲缘种）的内源性Mce1脂质导入蛋白的冷冻电镜（cryo-EM）结构。该结构揭示了Mce1系统的蛋白质是如何组装成一个细长的ABC转运体复合物的，该复合物的长度足以跨越细胞包膜。Mce1复合物由一个弯曲的针状结构域主导，该结构域似乎与之前描述的蛋白质结构无关，它为脂质跨包膜运输创造了一个受保护的疏水性途径。

这些结构数据揭示了Mce1复合物亚基的存在，研究人员结合冷冻电镜和AlphaFold2对其进行了鉴定，并将其命名为LucB。这些数据为Mce1介导的脂质跨分枝杆菌细胞包膜输入建立了一个结构模型。

附：英文原文

Title: Structure of an endogenous mycobacterial MCE lipid transporter

Author: Chen, James, Fruhauf, Alice, Fan, Catherine, Ponce, Jackeline, Ueberheide, Beatrix, Bhabha, Gira, Ekiert, Damian C.

Issue&Volume: 2023-07-26

Abstract: To replicate inside macrophages and cause tuberculosis, Mycobacterium tuberculosis must scavenge a variety of nutrients from the host1,2. The mammalian cell entry (MCE) proteins are important virulence factors in M. tuberculosis1,3, where they are encoded by large gene clusters and have been implicated in the transport of fatty acids4,5,6,7 and cholesterol1,4,8 across the impermeable mycobacterial cell envelope. Very little is known about how cargos are transported across this barrier, and it remains unclear how the approximately ten proteins encoded by a mycobacterial mce gene cluster assemble to transport cargo across the cell envelope. Here we report the cryo-electron microscopy (cryo-EM) structure of the endogenous Mce1 lipid-import machine of Mycobacterium smegmatis—a non-pathogenic relative of M. tuberculosis. The structure reveals how the proteins of the Mce1 system assemble to form an elongated ABC transporter complex that is long enough to span the cell envelope. The Mce1 complex is dominated by a curved, needle-like domain that appears to be unrelated to previously described protein structures, and creates a protected hydrophobic pathway for lipid transport across the periplasm. Our structural data revealed the presence of a subunit of the Mce1 complex, which we identified using a combination of cryo-EM and AlphaFold2, and name LucB. Our data lead to a structural model for Mce1-mediated lipid import across the mycobacterial cell envelope.

DOI: 10.1038/s41586-023-06366-0

Source: https://www.nature.com/articles/s41586-023-06366-0

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html