8jl1
From Proteopedia
membrane proteins
Structural highlights
DiseaseHGNAT_HUMAN Retinitis pigmentosa;Sanfilippo syndrome type C. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. FunctionHGNAT_HUMAN Lysosomal acetyltransferase that acetylates the non-reducing terminal alpha-glucosamine residue of intralysosomal heparin or heparan sulfate, converting it into a substrate for luminal alpha-N-acetyl glucosaminidase.[1] [2] [3] [4] Publication Abstract from PubMedLysosomal transmembrane acetylation of heparan sulfates (HS) is catalyzed by HS acetyl-CoA:alpha-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. 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 Nat Struct Mol Biol. 2024 Oct;31(10):1502-1508. doi: 10.1038/s41594-024-01315-5. , Epub 2024 May 20. PMID:38769387[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Homo sapiens | Large Structures | Ge JP | Xu RS | Yu J
