Structure of a SLC26 Anion Transporter STAS Domain in Complex with Acyl Carrier Protein: Implications for E. coli YchM in Fatty Acid Metabolism

SummaryEscherichia 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.

Graphical AbstractFigure optionsDownload high-quality image (402 K)Download as PowerPoint slideHighlights
► Crystal structure of the STAS domain of E. coli YchM in a complex with ACP
► YchM STAS structure predicts why mutations in SLC26A3 result in human disease
► Whole-genome synthetic lethal interactions links YchM to fatty acid (FA) metabolism
► Whole-cell physical interactions link YchM with proteins involved in FA metabolism