Ligand binding to the ACBD6 protein regulates the acyl-CoA transferase reactions in membranes

Eric Soupene,Frans A Kuypers

doi:10.1194/jlr.m061937

Abstract

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.

Highlights

The binding determinants of the human acyl-CoA binding domain-containing protein (ACBD) 6 and its function in lipid renewal of membranes were investigated
We show that ACBD6-bound acyl-CoAs were the substrates for the lysophospholipid acyltransferase enzymes and that ACBD6 controls the rate of acylation in membranes by the Lands’ pathway enzymes
Acyl-CoA binding to ACBD6 was dependent on the ligand and protein concentration (Fig. 1A)

Summary

Introduction

The binding determinants of the human acyl-CoA binding domain-containing protein (ACBD) 6 and its function in lipid renewal of membranes were investigated. 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.—Soupene, E., and F. Human ACBD6 is a modular protein with an N-terminal domain carrying the acyl-CoA binding domain and a carboxy-terminal domain with two ankyrin repeats, predicted to function as anchor motif to other proteins [25] This nonconserved C-terminus domain, present in members ACBD2 to ACBD6, is lacking in ACBD1 and ACBD7.

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