8IZD

Cryo-EM structure of the C26-CoA-bound Lac1-Lip1 complex

Summary for 8IZD

• Entry DOI: 10.2210/pdb8izd/pdb
• EMDB information: 35862
• Descriptor: Ceramide synthase LAC1, Ceramide synthase subunit LIP1, (4S,7R)-4-HYDROXY-N,N,N-TRIMETHYL-9-OXO-7-[(PALMITOYLOXY)METHYL]-3,5,8-TRIOXA-4-PHOSPHAHEXACOSAN-1-AMINIUM 4-OXIDE, ... (4 entities in total)
• Functional Keywords: substrate, complex, transferase
• Biological source: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (baker's yeast); More
• Total number of polymer chains: 4
• Total formula weight: 141906.55

Authors

Xie, T.,Fang, Q.,Gong, X. (deposition date: 2023-04-07, release date: 2023-12-13, Last modification date: 2024-10-16)

Primary citation

Xie, T.,Fang, Q.,Zhang, Z.,Wang, Y.,Dong, F.,Gong, X.
Structure and mechanism of a eukaryotic ceramide synthase complex.
Embo J., 42:e114889-e114889, 2023

PubMed Abstract: Ceramide synthases (CerS) catalyze ceramide formation via N-acylation of a sphingoid base with a fatty acyl-CoA and are attractive drug targets for treating numerous metabolic diseases and cancers. Here, we present the cryo-EM structure of a yeast CerS complex, consisting of a catalytic Lac1 subunit and a regulatory Lip1 subunit, in complex with C26-CoA substrate. The CerS holoenzyme exists as a dimer of Lac1-Lip1 heterodimers. Lac1 contains a hydrophilic reaction chamber and a hydrophobic tunnel for binding the CoA moiety and C26-acyl chain of C26-CoA, respectively. Lip1 interacts with both the transmembrane region and the last luminal loop of Lac1 to maintain the proper acyl chain binding tunnel. A lateral opening on Lac1 serves as a potential entrance for the sphingoid base substrate. Our findings provide a template for understanding the working mechanism of eukaryotic ceramide synthases and may facilitate the development of therapeutic CerS modulators.

PubMed: 37953642
DOI: 10.15252/embj.2023114889

Experimental method

ELECTRON MICROSCOPY (3.09 Å)