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Open data
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Basic information
| Entry | Database: PDB / ID: 8jkv | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Title | membrane proteins | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Components | Heparan-alpha-glucosaminide N-acetyltransferase | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Keywords | MEMBRANE PROTEIN / enzyme / acetylation | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Function / homology | Function and homology informationheparan-alpha-glucosaminide N-acetyltransferase / heparan-alpha-glucosaminide N-acetyltransferase activity / MPS IIIC - Sanfilippo syndrome C / heparan sulfate proteoglycan catabolic process / HS-GAG degradation / lysosomal transport / acyltransferase activity / protein complex oligomerization / tertiary granule membrane / specific granule membrane ...heparan-alpha-glucosaminide N-acetyltransferase / heparan-alpha-glucosaminide N-acetyltransferase activity / MPS IIIC - Sanfilippo syndrome C / heparan sulfate proteoglycan catabolic process / HS-GAG degradation / lysosomal transport / acyltransferase activity / protein complex oligomerization / tertiary granule membrane / specific granule membrane / lysosomal lumen / lysosomal membrane / Neutrophil degranulation / plasma membrane Similarity search - Function | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Biological species | Homo sapiens (human) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.87 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Authors | Yu, J. / Ge, J.P. / Ruisheng, X. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Funding support | China, 1items
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Citation | Journal: Nat Struct Mol Biol / Year: 2024Title: Structure and mechanism of lysosome transmembrane acetylation by HGSNAT. Authors: Ruisheng Xu / Yingjie Ning / Fandong Ren / Chenxia Gu / Zhengjiang Zhu / Xuefang Pan / Alexey V Pshezhetsky / Jingpeng Ge / Jie Yu / ![]() 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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 8jkv.cif.gz | 240.9 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb8jkv.ent.gz | 193 KB | Display | PDB format |
| PDBx/mmJSON format | 8jkv.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Summary document | 8jkv_validation.pdf.gz | 1.5 MB | Display | wwPDB validaton report |
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| Full document | 8jkv_full_validation.pdf.gz | 1.5 MB | Display | |
| Data in XML | 8jkv_validation.xml.gz | 52.6 KB | Display | |
| Data in CIF | 8jkv_validation.cif.gz | 75.8 KB | Display | |
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/jk/8jkv ftp://data.pdbj.org/pub/pdb/validation_reports/jk/8jkv | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 36376MC ![]() 8jl1C ![]() 8jl3C ![]() 8w4aC M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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Components
-Protein , 1 types, 2 molecules AB
| #1: Protein | Mass: 77183.992 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: HGSNAT, TMEM76 / Production host: Homo sapiens (human)References: UniProt: Q68CP4, heparan-alpha-glucosaminide N-acetyltransferase |
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-Sugars , 2 types, 6 molecules 
| #2: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #3: Sugar | |
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-Non-polymers , 6 types, 66 molecules 










| #4: Chemical | ChemComp-D12 / #5: Chemical | ChemComp-OCT / #6: Chemical | ChemComp-C14 / #7: Chemical | #8: Chemical | #9: Chemical | |
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-Details
| Has ligand of interest | N |
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| Has protein modification | Y |
-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
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| EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
| Component | Name: HG / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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| Source (natural) | Organism: Homo sapiens (human) |
| Source (recombinant) | Organism: Homo sapiens (human) |
| Buffer solution | pH: 8 |
| Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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| Microscopy | Model: FEI TITAN KRIOS |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 800 nm |
| Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
| EM software | Name: PHENIX / Category: model refinement | ||||||||||||||||||||||||
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| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
| 3D reconstruction | Resolution: 2.87 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 715945 / Symmetry type: POINT | ||||||||||||||||||||||||
| Refine LS restraints |
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About Yorodumi




Homo sapiens (human)
China, 1items
Citation







PDBj









FIELD EMISSION GUN