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| Title | Structure and mechanism of lysosome transmembrane acetylation by HGSNAT. |
|---|---|
| Journal, issue, pages | Nat Struct Mol Biol, Vol. 31, Issue 10, Page 1502-1508, Year 2024 |
| Publish date | May 20, 2024 |
Authors | Ruisheng Xu / Yingjie Ning / Fandong Ren / Chenxia Gu / Zhengjiang Zhu / Xuefang Pan / Alexey V Pshezhetsky / Jingpeng Ge / Jie Yu / ![]() |
| 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 ...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. |
External links | Nat Struct Mol Biol / PubMed:38769387 |
| Methods | EM (single particle) |
| Resolution | 2.59 - 2.87 Å |
| Structure data | EMDB-36376, PDB-8jkv: EMDB-36386, PDB-8jl1: EMDB-36387, PDB-8jl3: EMDB-37264, PDB-8w4a: |
| Chemicals | ![]() ChemComp-NAG: ![]() ChemComp-D12: ![]() ChemComp-OCT: ![]() ChemComp-C14: ![]() ChemComp-CLR: ![]() ChemComp-D10: ![]() ChemComp-R16: ![]() ChemComp-ACO: ![]()
ChemComp-UV6: ![]() ChemComp-HP6: |
| Source |
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Keywords | MEMBRANE PROTEIN / enzyme / acetylation |
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homo sapiens (human)
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