Ligand binding to the ACBD6 protein regulates the acyl-CoA transferase reactions in membranes.
The binding determinants of the human acyl-CoA binding domain-containing protein (ACBD) 6 and its function in lipid renewal of membranes were investigated. ACBD6 binds acyl-CoAs of a chain length of 6 to 20 carbons. The stoichiometry of the association could not be fitted to a 1-to-1 model. Saturation of ACBD6 by C16:0-CoA required higher concentration than less abundant acyl-CoAs. In contrast to ACBD1 and ACBD3, ligand binding did not result in the dimerization of ACBD6. The presence of fatty acids affected the binding of C18:1-CoA to ACBD6, dependent on the length, the degree of unsaturation, and the stereoisomeric conformation of their aliphatic chain. ACBD1 and ACBD6 negatively affected the formation of phosphatidylcholine (PC) and phosphatidylethanolamine in the red blood cell membrane. The acylation rate of lysophosphatidylcholine into PC catalyzed by the red cell lysophosphatidylcholine-acyltransferase 1 protein was limited by the transfer of the acyl-CoA substrate from ACBD6 to the acyltransferase enzyme. These findings provide evidence that the binding properties of ACBD6 are adapted to prevent its constant saturation by the very abundant C16:0-CoA and protect membrane systems from the detergent nature of free acyl-CoAs by controlling their release to acyl-CoA-utilizing enzymes.
Children's Hospital Oakland Research Institute, Oakland, CA 94609.
Eric
E
Soupene
Children's Hospital Oakland Research Institute, Oakland, CA 94609.
Frans A
FA
Kuypers
D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000378:metabolism; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000214:Acyl Coenzyme A / Q000378:metabolism; D000215:Acylation; D000595:Amino Acid Sequence; D001667:Binding, Competitive; D003001:Cloning, Molecular; D015256:Coenzyme A-Transferases / Q000378:metabolism*; D017124:Conserved Sequence; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D008024:Ligands; D050356:Lipid Metabolism; D008566:Membranes / Q000201:enzymology / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D011485:Protein Binding
C530903:ACBD6 protein, human; D018528:ATP-Binding Cassette Transporters; D000214:Acyl Coenzyme A; D005227:Fatty Acids; D008024:Ligands; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C483858:phosphatidylethanolamine; D008243:1-Acylglycerophosphocholine O-Acyltransferase; C526202:Lpcat1 protein, human; D015256:Coenzyme A-Transferases; C031212:acyl-CoA transferase
acyl-coenzyme A; acyl-coenzyme A binding domain-containing protein 6; binding protein; erythrocyte; fatty acids; lipids; phospholipids