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

ABSTRACT: 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.

SUBMITTER: Rana MS

PROVIDER: S-EPMC6317078 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Fatty acyl recognition and transfer by an integral membrane <i>S</i>-acyltransferase.

Rana Mitra S MS Kumar Pramod P Lee Chul-Jin CJ Verardi Raffaello R Rajashankar Kanagalaghatta R KR Banerjee Anirban A Banerjee Anirban A

Science (New York, N.Y.) 20180101 6372

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-exc ...[more]

PMID: 29326245

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