EMD-37264

Single-particle
2.69 Å
EMD-37264 Deposition: 23/08/2023
Map released: 23/10/2024
Last modified: 13/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-37264

membrane proteins

EMD-37264

Single-particle
2.69 Å
EMD-37264 Deposition: 23/08/2023
Map released: 23/10/2024
Last modified: 13/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens
Sample: HGSNAT
Fitted models: 8w4a (Avg. Q-score: 0.619)

Deposition Authors: Yu J , Ge JP, Xu RS
Structure and mechanism of lysosome transmembrane acetylation by HGSNAT.
Xu R, Ning Y, Ren F, Gu C, Zhu Z , Pan X, Pshezhetsky AV , Ge J , Yu J
(2024) Nat Struct Mol Biol , 31 , 1502 - 1508
PUBMED: 38769387
DOI: doi:10.1038/s41594-024-01315-5
ISSN: 1545-9985
Abstract:
Lysosomal transmembrane acetylation of heparan sulfates (HS) is catalyzed by HS acetyl-CoA:α-glucosaminide N-acetyltransferase (HGSNAT), whose dysfunction leads to lysosomal storage diseases. The mechanism by which HGSNAT, the sole non-hydrolase enzyme in HS degradation, brings cytosolic acetyl-coenzyme A (Ac-CoA) and lysosomal HS together for N-acyltransferase reactions remains unclear. Here, we present cryogenic-electron microscopy structures of HGSNAT alone, complexed with Ac-CoA and with acetylated products. These structures explain that Ac-CoA binding from the cytosolic side causes dimeric HGSNAT to form a transmembrane tunnel. Within this tunnel, catalytic histidine and asparagine approach the lumen and instigate the transfer of the acetyl group from Ac-CoA to the glucosamine group of HS. Our study unveils a transmembrane acetylation mechanism that may help advance therapeutic strategies targeting lysosomal storage diseases.