Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S3E1, Canada.
Structure. 2010 Nov 10;18(11):1450-62. doi: 10.1016/j.str.2010.08.015.
Escherichia coli YchM is a member of the SLC26 (SulP) family of anion transporters with an N-terminal membrane domain and a C-terminal cytoplasmic STAS domain. Mutations in human members of the SLC26 family, including their STAS domain, are linked to a number of inherited diseases. Herein, we describe the high-resolution crystal structure of the STAS domain from E. coli YchM isolated in complex with acyl-carrier protein (ACP), an essential component of the fatty acid biosynthesis (FAB) pathway. A genome-wide genetic interaction screen showed that a ychM null mutation is synthetically lethal with mutant alleles of genes (fabBDHGAI) involved in FAB. Endogenous YchM also copurified with proteins involved in fatty acid metabolism. Furthermore, a deletion strain lacking ychM showed altered cellular bicarbonate incorporation in the presence of NaCl and impaired growth at alkaline pH. Thus, identification of the STAS-ACP complex suggests that YchM sequesters ACP to the bacterial membrane linking bicarbonate transport with fatty acid metabolism.
大肠杆菌 YchM 是 SLC26（SulP）家族阴离子转运蛋白的成员，具有 N 端膜结构域和 C 端胞质 STAS 结构域。人类 SLC26 家族成员及其 STAS 结构域的突变与多种遗传性疾病有关。本文描述了大肠杆菌 YchM 的 STAS 结构域与酰基载体蛋白（ACP）的高分辨率晶体复合物结构，ACP 是脂肪酸生物合成（FAB）途径的必需成分。全基因组遗传相互作用筛选表明，ychM 缺失突变与参与 FAB 的基因（fabBDHGAI）的突变等位基因在合成上是致死的。内源性 YchM 也与参与脂肪酸代谢的蛋白质共纯化。此外，缺乏 ychM 的缺失株在存在 NaCl 的情况下表现出细胞内碳酸氢盐掺入的改变，并在碱性 pH 下生长受损。因此，STAS-ACP 复合物的鉴定表明 YchM 将 ACP 隔离在细菌膜上，将碳酸氢盐转运与脂肪酸代谢联系起来。
