Department of Biochemistry and Molecular Biology and the Center for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
Nat Commun. 2018 Mar 20;9(1):1159. doi: 10.1038/s41467-018-03547-8.
Undecaprenyl pyrophosphate phosphatase (UppP) is an integral membrane protein that recycles the lipid carrier essential to the ongoing biosynthesis of the bacterial cell wall. Individual building blocks of peptidoglycan are assembled in the cytoplasm on undecaprenyl phosphate (C55-P) before being flipped to the periplasmic face, where they are polymerized and transferred to the existing cell wall sacculus, resulting in the side product undecaprenyl pyrophosphate (C55-PP). Interruption of UppP's regeneration of C55-P from C55-PP leads to the buildup of cell wall intermediates and cell lysis. We present the crystal structure of UppP from Escherichia coli at 2.0 Å resolution, which reveals the mechanistic basis for intramembranal phosphatase action and substrate specificity using an inverted topology repeat. In addition, the observation of key structural motifs common to a variety of cross membrane transporters hints at a potential flippase function in the specific relocalization of the C55-P product back to the cytosolic space.
十一烯基焦磷酸磷酸酶（UppP）是一种膜内在蛋白，可循环利用脂质载体，该脂质载体对细菌细胞壁的持续生物合成至关重要。肽聚糖的单个构建块在细胞质中与十一烯基磷酸（C55-P）组装，然后翻转到周质面，在那里它们聚合并转移到现有的细胞壁囊泡中，从而产生副产物十一烯基焦磷酸（C55-PP）。UppP 不能将 C55-PP 再生为 C55-P，会导致细胞壁中间产物的积累和细胞裂解。我们展示了来自大肠杆菌的 UppP 的 2.0Å 分辨率晶体结构，该结构揭示了使用反转拓扑重复的跨膜磷酸酶作用和底物特异性的机制基础。此外，观察到各种跨膜转运蛋白共有的关键结构基序，提示其在 C55-P 产物特异性重新定位回细胞质空间方面具有潜在的翻转酶功能。
