Association of NMT2 with the acyl-CoA carrier ACBD6 protects the N-myristoyltransferase reaction from palmitoyl-CoA

作者：Soupene Eric^*; Kao Joseph; Cheng Daniel H; Wang Derek; Greninger Alexander L; Knudsen Giselle M; DeRisi Joseph L; Kuypers Frans A

来源：The Journal of Lipid Research, 2016, 57(2): 288-298.

DOI：10.1194/jlr.M065003

• protein acylation
• membranes
• phospholipids
• binding protein
• protein interaction
• N-myristoyltransferase 2
• coenzyme A

The covalent attachment of a 14-carbon aliphatic tail on a glycine residue of nascent translated peptide chains is catalyzed in human cells by two N-myristoyltransferase (NMT) enzymes using the rare myristoyl-CoA (C-14-CoA) molecule as fatty acid donor. Although, NMT enzymes can only transfer a myristate group, they lack specificity for C-14 CoA and can also bind the far more abundant palmitoylCoA (C-16-CoA) molecule. We determined that the acyl-CoA binding protein, acyl-CoA binding domain (ACBD) 6, stimulated the NMT reaction of NMT2. This stimulatory effect required interaction between ACBD6 and NMT2, and was enhanced by binding of ACBD6 to its ligand, C-18:2-CoA. ACBD6 also interacted with the second human NMT enzyme, NMT1. The presence of ACBD6 prevented competition of the NMT reaction by C-16-CoA. Mutants of ACBD6 that were either deficient in ligand binding to the N-terminal ACBD or unable to interact with NMT2 did not stimulate activity of NMT2, nor could they protect the enzyme from utilizing the competitor C-16-CoA. These results indicate that ACBD6 can locally sequester C-16-CoA and prevent its access to the enzyme binding site via interaction with NMT2. Thus, the ligand binding properties of the NMT/ACBD6 complex can explain how the NMT reaction can proceed in the presence of the very abundant competitive substrate, C-16-CoA.

• 出版日期2016-2