+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-36387 | |||||||||
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Title | membrane proteins | |||||||||
Map data | ||||||||||
Sample |
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Keywords | enzyme / acetylation / MEMBRANE PROTEIN | |||||||||
Function / homology | Function and homology information 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 ...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 | single particle reconstruction / cryo EM / Resolution: 2.59 Å | |||||||||
Authors | Yu J / Ge JP / Xu RS | |||||||||
Funding support | China, 1 items
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Citation | Journal: Nat Struct Mol Biol / Year: 2024 Title: 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. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_36387.map.gz | 230 MB | EMDB map data format | |
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Header (meta data) | emd-36387-v30.xml emd-36387.xml | 16 KB 16 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_36387_fsc.xml | 13.2 KB | Display | FSC data file |
Images | emd_36387.png | 92.7 KB | ||
Filedesc metadata | emd-36387.cif.gz | 5.9 KB | ||
Others | emd_36387_half_map_1.map.gz emd_36387_half_map_2.map.gz | 226.5 MB 226.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-36387 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36387 | HTTPS FTP |
-Validation report
Summary document | emd_36387_validation.pdf.gz | 797.2 KB | Display | EMDB validaton report |
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Full document | emd_36387_full_validation.pdf.gz | 796.7 KB | Display | |
Data in XML | emd_36387_validation.xml.gz | 21.7 KB | Display | |
Data in CIF | emd_36387_validation.cif.gz | 27.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36387 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36387 | HTTPS FTP |
-Related structure data
Related structure data | 8jl3MC 8jkvC 8jl1C 8w4aC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_36387.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.83 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_36387_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_36387_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : HGSNAT
+Supramolecule #1: HGSNAT
+Macromolecule #1: Heparan-alpha-glucosaminide N-acetyltransferase
+Macromolecule #3: 2-acetamido-2-deoxy-beta-D-glucopyranose
+Macromolecule #4: ACETYL COENZYME *A
+Macromolecule #5: DODECANE
+Macromolecule #6: N-OCTANE
+Macromolecule #7: TETRADECANE
+Macromolecule #8: CHOLESTEROL
+Macromolecule #9: DECANE
+Macromolecule #10: HEXADECANE
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |