2. Academic Validation
  3. Fatty acyl recognition and transfer by an integral membrane S-acyltransferase

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

  • Science. 2018 Jan 12;359(6372):eaao6326. doi: 10.1126/science.aao6326.
Mitra S Rana 1,  Pramod Kumar 1,  Chul-Jin Lee 1,  Raffaello Verardi 1,  Kanagalaghatta R Rajashankar 2,  Anirban Banerjee 1
Affiliations

Affiliations

  • 1 Cell Biology and Neurobiology Branch, National Institutes of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
  • 2 Northeastern Collaborative Access Team (NE-CAT) and Department of Chemistry and Chemical Biology, Cornell University, Building 436E, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, IL 60439, USA.
PMID: 29326245 DOI: 10.1126/science.aao6326
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.

Figures