Structure of a SLC26 anion transporter STAS domain in complex with acyl carrier protein: implications for E. coli YchM in fatty acid metabolism.
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.
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.
Mohan
M
Babu
Jack F
JF
Greenblatt
Andrew
A
Emili
Natalie C J
NC
Strynadka
Reinhart A F
RA
Reithmeier
Trevor F
TF
Moraes
D000213:Acyl Carrier Protein / Q000737:chemistry* / Q000378:metabolism; D027321:Anion Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D003461:Crystallography; D004926:Escherichia coli / Q000737:chemistry* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D047468:Immunoprecipitation; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D046912:Multiprotein Complexes / Q000737:chemistry*; D009154:Mutation / Q000235:genetics; D017434:Protein Structure, Tertiary; D000076988:Sulfate Transporters
D000213:Acyl Carrier Protein; D027321:Anion Transport Proteins; D029968:Escherichia coli Proteins; D005227:Fatty Acids; D046912:Multiprotein Complexes; C473560:SLC26A1 protein, human; D000076988:Sulfate Transporters; C556152:YchM protein, E coli