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Open data
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Basic information
| Entry | ![]() | |||||||||
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| Title | Focus refinement of HURP-alpha-beta-tubulin | |||||||||
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Sample |
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Keywords | HURP / tubulin / mitosis / CELL CYCLE | |||||||||
| Biological species | Homo sapiens (human) | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.54 Å | |||||||||
Authors | Chen PP / Hsia KC | |||||||||
| Funding support | Taiwan, 1 items
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Citation | Journal: Nat Commun / Year: 2024Title: HURP binding to the vinca domain of β-tubulin accounts for cancer drug resistance. Authors: Athira Saju / Po-Pang Chen / Tzu-Han Weng / Su-Yi Tsai / Akihiro Tanaka / Yu-Ting Tseng / Chih-Chia Chang / Chun-Hsiung Wang / Yuta Shimamoto / Kuo-Chiang Hsia / ![]() Abstract: Vinca alkaloids, a class of tubulin-binding agent, are widely used in treating cancer, yet the emerging resistance compromises their efficacy. Hepatoma up-regulated protein (HURP), a microtubule- ...Vinca alkaloids, a class of tubulin-binding agent, are widely used in treating cancer, yet the emerging resistance compromises their efficacy. Hepatoma up-regulated protein (HURP), a microtubule-associated protein displaying heightened expression across various cancer types, reduces cancer cells' sensitivity to vinca-alkaloid drugs upon overexpression. However, the molecular basis behind this drug resistance remains unknown. Here we discover a tubulin-binding domain within HURP, and establish its role in regulating microtubule growth. Cryo-EM analysis reveals interactions between HURP's tubulin-binding domain and the vinca domain on β-tubulin -- the site targeted by vinca alkaloid drugs. Importantly, HURP competes directly with vinorelbine, a vinca alkaloid-based chemotherapeutic agent, countering microtubule growth defects caused by vinorelbine both in vitro and in vivo. Our findings elucidate a mechanism driving drug resistance in HURP-overexpressing cancer cells and emphasize HURP tubulin-binding domain's role in mitotic spindle assembly. This underscores its potential as a therapeutic target to improve cancer treatment. | |||||||||
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Structure visualization
| Supplemental images |
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Downloads & links
-EMDB archive
| Map data | emd_38179.map.gz | 59.7 MB | EMDB map data format | |
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| Header (meta data) | emd-38179-v30.xml emd-38179.xml | 11.6 KB 11.6 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_38179_fsc.xml | 8.5 KB | Display | FSC data file |
| Images | emd_38179.png | 106.5 KB | ||
| Filedesc metadata | emd-38179.cif.gz | 3.8 KB | ||
| Others | emd_38179_half_map_1.map.gz emd_38179_half_map_2.map.gz | 59.1 MB 59.1 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-38179 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-38179 | HTTPS FTP |
-Validation report
| Summary document | emd_38179_validation.pdf.gz | 727.8 KB | Display | EMDB validaton report |
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| Full document | emd_38179_full_validation.pdf.gz | 727.4 KB | Display | |
| Data in XML | emd_38179_validation.xml.gz | 16.2 KB | Display | |
| Data in CIF | emd_38179_validation.cif.gz | 21 KB | Display | |
| Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-38179 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-38179 | HTTPS FTP |
-Related structure data
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Map
| File | Download / File: emd_38179.map.gz / Format: CCP4 / Size: 64 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: #2
| File | emd_38179_half_map_1.map | ||||||||||||
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| Density Histograms |
-Half map: #1
| File | emd_38179_half_map_2.map | ||||||||||||
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| Density Histograms |
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Sample components
-Entire : HURP-alpha-beta-tubulin
| Entire | Name: HURP-alpha-beta-tubulin |
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| Components |
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-Supramolecule #1: HURP-alpha-beta-tubulin
| Supramolecule | Name: HURP-alpha-beta-tubulin / type: complex / ID: 1 / Parent: 0 |
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| Source (natural) | Organism: Homo sapiens (human) |
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Buffer | pH: 7.4 |
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| Vitrification | Cryogen name: ETHANE |
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Electron microscopy
| Microscope | FEI TITAN KRIOS |
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| Image recording | Film or detector model: GATAN K3 BIOQUANTUM (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: 2.5 µm / Nominal defocus min: 1.2 µm |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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About Yorodumi




Keywords
Homo sapiens (human)
Authors
Taiwan, 1 items
Citation




Z (Sec.)
Y (Row.)
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Processing
FIELD EMISSION GUN

