Open AccessBivalent recognition of fatty acyl-CoA by a human integral membrane palmitoyltransferase
Author(s) -
ChulJin Lee,
Robyn Stix,
Mitra S. Rana,
Flowreen Shikwana,
Murphy Ra,
Rodolfo Ghirlando,
José D. Faráldo-Gómez,
Anirban Banerjee
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2022050119
Subject(s) - palmitoylation , thioester , biochemistry , chemistry , bivalent (engine) , enzyme , integral membrane protein , biology , microbiology and biotechnology , membrane protein , membrane , cysteine , organic chemistry , metal
Significance Protein palmitoylation is one of the most highly abundant protein modifications, through which long-chain fatty acids get attached to cysteines by a thioester linkage. It plays critically important roles in growth signaling, the organization of synaptic receptors, and the regulation of ion channel function. Yet the molecular mechanism of the DHHC family of integral membrane enzymes that catalyze this modification remains poorly understood. Here, we present the structure of a precatalytic complex of human DHHC20 with palmitoyl CoA. Together with the accompanying functional data, the structure shows how a bivalent recognition of palmitoyl CoA by the DHHC enzyme, simultaneously at both the fatty acyl group and the CoA headgroup, is essential for catalytic chemistry to proceed.