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分枝杆菌ABC转运体介导亲水化合物的吸收
2020-03-29 23:41

荷兰格罗宁根大学D. J. Slotboom、A. Guskov和美国SLAC国家加速器实验室C. Gati合作发现结核分枝杆菌(Mtb)ABC转运蛋白介导亲水性化合物的吸收。该项研究成果在线发表在2020年3月25日出版的《自然》杂志上。

通过解析Rv1819c的结构,研究人员发现Rv1819c蛋白的确包含ATP结合盒(ABC)-转运折叠,以及约7700Å的水腔,这使其能够运输无关的亲水性化合物博来霉素和钴胺素。基于这些结构,研究人员猜测Rv1819c是亲水分子的多溶质转运蛋白,类似于ABC转运蛋白家族的多药转运蛋白,它从细胞中转运出结构多样的疏水化合物。

研究人员表示,结核分枝杆菌是特异的人类致病菌,是结核病的病原体。尽管Mtb可以从头合成维生素B12(钴胺素),但钴胺素的摄取与结核病的发病机理有关。Mtb不编码任何特定的钴胺素转运蛋白;但之前研究表明rv1819c基因对于摄取钴胺素必不可少。这个发现与最初报道Rv1819c的功能不吻合,因为Rv1819c是与抗菌肽(如博来霉素)运输有关的蛋白质。此外,钴胺素的摄取似乎与氨基酸序列不一致,这表明Rv1819c具有细菌ABC-转运折叠。

附:英文原文

Title: A mycobacterial ABC transporter mediates the uptake of hydrophilic compounds

Author: S. Rempel, C. Gati, M. Nijland, C. Thangaratnarajah, A. Karyolaimos, J. W. de Gier, A. Guskov, D. J. Slotboom

Issue&Volume: 2020-03-25

Abstract: Mycobacterium tuberculosis (Mtb) is an obligate human pathogen and the causative agent of tuberculosis1,2,3. Although Mtb can synthesize vitamin B12 (cobalamin) de novo, uptake of cobalamin has been linked to pathogenesis of tuberculosis2. Mtb does not encode any characterized cobalamin transporter4,5,6; however, the gene rv1819c was found to be essential for uptake of cobalamin1. This result is difficult to reconcile with the original annotation of Rv1819c as a protein implicated in the transport of antimicrobial peptides such as bleomycin7. In addition, uptake of cobalamin seems inconsistent with the amino acid sequence, which suggests that Rv1819c has a bacterial ATP-binding cassette (ABC)-exporter fold1. Here, we present structures of Rv1819c, which reveal that the protein indeed contains the ABC-exporter fold, as well as a large water-filled cavity of about 7,700 3, which enables the protein to transport the unrelated hydrophilic compounds bleomycin and cobalamin. On the basis of these structures, we propose that Rv1819c is a multi-solute transporter for hydrophilic molecules, analogous to the multidrug exporters of the ABC transporter family, which pump out structurally diverse hydrophobic compounds from cells8,9,10,11.

DOI: 10.1038/s41586-020-2072-8

Source: https://www.nature.com/articles/s41586-020-2072-8

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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