小柯机器人

美国哈佛医学院David Z. Rudner研究小组发现两个广泛保守的聚异戊二烯磷酸转运体家族。该项研究成果于2022年11月30日在线发表在《自然》杂志上。

研究人员利用针对十一异戊烯磷酸（UndP）的抗生素amphomycin，发现了两个影响UndP回收的广泛保守蛋白家族。其中一个（UptA）是DedA超家族的成员；另一个（PopT）含有DUF368结构域。遗传学、细胞学和合成分析认为，这些蛋白是缺失的UndP运输器。重要的是，来自革兰氏阳性和革兰氏阴性细菌的同系物促进了枯草杆菌中UndP的运输，表明循环活性在家族成员中广泛保守。这些翻转酶的抑制剂可以增强目前针对细胞包膜的抗生素库。

据介绍，肽聚糖和细菌中几乎所有的表面糖聚合物都是在细胞质中建立在脂质载体UndP上的。这些与UndP相连的前体被运过膜并聚合或直接转移到表面聚合物、脂类或蛋白质上。然后UndP被翻转，从而再生面向细胞质的UndP池。几十年来，催化运输的翻转酶身份一直没有得到确认。

附：英文原文

Title: Two broadly conserved families of polyprenyl-phosphate transporters

Author: Roney, Ian J., Rudner, David Z.

Issue&Volume: 2022-11-30

Abstract: Peptidoglycan and virtually all surface glycopolymers in bacteria are built in the cytoplasm on the lipid carrier undecaprenyl-phosphate (UndP)1–4. These UndP-linked precursors are transported across the membrane and polymerized or directly transferred to surface polymers, lipids, or proteins. UndP is then flipped to regenerate the pool of cytoplasmic-facing UndP. The identity of the flippase that catalyzes transport has eluded identification for decades. Here, using the antibiotic amphomycin that targets UndP5–7, we discovered two broadly conserved protein families that affect UndP recycling. One (UptA) is a member of the DedA superfamily8; the other (PopT) contains the domain DUF368. Genetic, cytological, and syntenic analyses argue that these proteins are the missing UndP transporters. Importantly, homologs from gram-positive and gram-negative bacteria promote UndP transport in Bacillus subtilis, indicating that recycling activity is broadly conserved among family members. Inhibitors of these flippases could potentiate the current arsenal of cell envelope-targeting antibiotics.

DOI: 10.1038/s41586-022-05587-z

Source: https://www.nature.com/articles/s41586-022-05587-z

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