Fatty acyl recognition and transfer by an integral membrane S-acyltransferase.

Mitra S Rana, Pramod Kumar, Chul-Jin Lee, Raffaello Verardi, Kanagalaghatta R Rajashankar, Anirban Banerjee

Science (New York, N.Y.) 2018 Jan 12

filter terms:

DHHC (Asp-His-His-Cys) palmitoyltransferases are eukaryotic integral membrane enzymes that catalyze protein palmitoylation, which is important in a range of physiological processes, including small guanosine triphosphatase (GTPase) signaling, cell adhesion, and neuronal receptor scaffolding. We present crystal structures of two DHHC palmitoyltransferases and a covalent intermediate mimic. The active site resides at the membrane-cytosol interface, which allows the enzyme to catalyze thioester-exchange chemistry by using fatty acyl-coenzyme A and explains why membrane-proximal cysteines are candidates for palmitoylation. The acyl chain binds in a cavity formed by the transmembrane domain. We propose a mechanism for acyl chain-length selectivity in DHHC enzymes on the basis of cavity mutants with preferences for shorter and longer acyl chains. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Citation

Mitra S Rana, Pramod Kumar, Chul-Jin Lee, Raffaello Verardi, Kanagalaghatta R Rajashankar, Anirban Banerjee. Fatty acyl recognition and transfer by an integral membrane S-acyltransferase. Science (New York, N.Y.). 2018 Jan 12;359(6372)