8JL3

membrane proteins

Summary for 8JL3

• Entry DOI: 10.2210/pdb8jl3/pdb
• EMDB information: 36387
• Descriptor: Heparan-alpha-glucosaminide N-acetyltransferase, HEXADECANE, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (10 entities in total)
• Functional Keywords: enzyme, acetylation, membrane protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 169518.97

Authors

Yu, J.,Ge, J.P.,Xu, R.S. (deposition date: 2023-06-02, release date: 2024-05-22, Last modification date: 2024-10-30)

Primary citation

Xu, R.,Ning, Y.,Ren, F.,Gu, C.,Zhu, Z.,Pan, X.,Pshezhetsky, A.V.,Ge, J.,Yu, J.
Structure and mechanism of lysosome transmembrane acetylation by HGSNAT.
Nat.Struct.Mol.Biol., 31:1502-1508, 2024

PubMed 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.

PubMed: 38769387
DOI: 10.1038/s41594-024-01315-5

Experimental method

ELECTRON MICROSCOPY (2.59 Å)