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- EMDB-38178: HURP (428-534)-alpha-tubulin-beta-tubulin complex -

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Basic information

Entry
Database: EMDB / ID: EMD-38178
TitleHURP (428-534)-alpha-tubulin-beta-tubulin complex
Map data
Sample
  • Complex: HURP (428-534)-alpha-tubulin-beta-tubulin complex
    • Protein or peptide: Tubulin alpha chain
    • Protein or peptide: Tubulin beta chain
    • Protein or peptide: Disks large-associated protein 5,Green fluorescent protein
KeywordsHURP / tubulin / drug resistance / mitosis / CELL CYCLE
Function / homology
Function and homology information


mitotic chromosome movement towards spindle pole / signaling / kinetochore assembly / positive regulation of mitotic metaphase/anaphase transition / spindle pole centrosome / NOTCH3 Intracellular Domain Regulates Transcription / centrosome localization / microtubule-based process / regulation of mitotic cell cycle / bioluminescence ...mitotic chromosome movement towards spindle pole / signaling / kinetochore assembly / positive regulation of mitotic metaphase/anaphase transition / spindle pole centrosome / NOTCH3 Intracellular Domain Regulates Transcription / centrosome localization / microtubule-based process / regulation of mitotic cell cycle / bioluminescence / mitotic spindle organization / generation of precursor metabolites and energy / chromosome segregation / structural constituent of cytoskeleton / microtubule cytoskeleton organization / neuron migration / mitotic spindle / mitotic cell cycle / microtubule binding / microtubule / hydrolase activity / GTPase activity / GTP binding / metal ion binding / nucleus / cytoplasm / cytosol
Similarity search - Function
SAPAP family / Guanylate-kinase-associated protein (GKAP) protein / Alpha tubulin / Tubulin-beta mRNA autoregulation signal. / Beta tubulin, autoregulation binding site / Beta tubulin / Green fluorescent protein, GFP / Tubulin / Tubulin, C-terminal / Tubulin C-terminal domain ...SAPAP family / Guanylate-kinase-associated protein (GKAP) protein / Alpha tubulin / Tubulin-beta mRNA autoregulation signal. / Beta tubulin, autoregulation binding site / Beta tubulin / Green fluorescent protein, GFP / Tubulin / Tubulin, C-terminal / Tubulin C-terminal domain / Tubulin, conserved site / Tubulin subunits alpha, beta, and gamma signature. / Green fluorescent protein-related / Green fluorescent protein / Green fluorescent protein / Tubulin/FtsZ family, C-terminal domain / Tubulin/FtsZ-like, C-terminal domain / Tubulin/FtsZ, C-terminal / Tubulin/FtsZ, 2-layer sandwich domain / Tubulin/FtsZ family, GTPase domain / Tubulin/FtsZ family, GTPase domain / Tubulin/FtsZ, GTPase domain / Tubulin/FtsZ, GTPase domain superfamily
Similarity search - Domain/homology
Tubulin alpha chain / Tubulin beta chain / Green fluorescent protein / Disks large-associated protein 5
Similarity search - Component
Biological speciesHomo sapiens (human) / Bos taurus (domestic cattle)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.54 Å
AuthorsChen P-P / Hsia K-C
Funding support Taiwan, 1 items
OrganizationGrant numberCountry
Academia Sinica (Taiwan)AS-IVA-112-L05 Taiwan
CitationJournal: Nat Commun / Year: 2024
Title: 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.
History
DepositionNov 30, 2023-
Header (metadata) releaseOct 23, 2024-
Map releaseOct 23, 2024-
UpdateJul 2, 2025-
Current statusJul 2, 2025Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

emd_38178.png

Downloads & links

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Map

FileDownload / File: emd_38178.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 256 pix.
= 212.48 Å		0.83 Å/pix.
x 256 pix.
= 212.48 Å		0.83 Å/pix.
x 256 pix.
= 212.48 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.83 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.25
Minimum - Maximum-0.9308383 - 1.7884995
Average (Standard dev.)-0.0015096499 (±0.043176826)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 212.48 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_38178_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_38178_half_map_2.map
Projections & Slices
AxesZYX

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Histogram

Histogram (log scale)

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Sample components

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Entire : HURP (428-534)-alpha-tubulin-beta-tubulin complex

EntireName: HURP (428-534)-alpha-tubulin-beta-tubulin complex
Components
  • Complex: HURP (428-534)-alpha-tubulin-beta-tubulin complex
    • Protein or peptide: Tubulin alpha chain
    • Protein or peptide: Tubulin beta chain
    • Protein or peptide: Disks large-associated protein 5,Green fluorescent protein

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Supramolecule #1: HURP (428-534)-alpha-tubulin-beta-tubulin complex

SupramoleculeName: HURP (428-534)-alpha-tubulin-beta-tubulin complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Tubulin alpha chain

MacromoleculeName: Tubulin alpha chain / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Bos taurus (domestic cattle)
Molecular weightTheoretical: 48.769988 KDa
Recombinant expressionOrganism: Bos taurus (domestic cattle)
SequenceString: MRECISIHVG QAGVQIGNAC WELYCLEHGI QPDGQMPSDK TIGGGDDSFN TFFSETGAGK HVPRAVFVDL EPTVIDEVRT GTYRQLFHP EQLITGKEDA ANNYARGHYT IGKEIIDLVL DRIRKLADQC TGLQGFSVFH SFGGGTGSGF TSLLMERLSV D YGKKSKLE ...String:
MRECISIHVG QAGVQIGNAC WELYCLEHGI QPDGQMPSDK TIGGGDDSFN TFFSETGAGK HVPRAVFVDL EPTVIDEVRT GTYRQLFHP EQLITGKEDA ANNYARGHYT IGKEIIDLVL DRIRKLADQC TGLQGFSVFH SFGGGTGSGF TSLLMERLSV D YGKKSKLE FSIYPAPQVS TAVVEPYNSI LTTHTTLEHS DCAFMVDNEA IYDICRRNLD IERPTYTNLN RLIGQIVSSI TA SLRFDGA LNVDLTEFQT NLVPYPRGHF PLATYAPVIS AEKAYHEQLS VAEITNACFE PANQMVKCDP RHGKYMACCL LYR GDVVPK DVNAAIATIK TKRTIQFVDW CPTGFKVGIN YEPPTVVPGG DLAKVQRAVC MLSNTTAIAE AWARLDHKFD LMYA KRAFV HWYVGEGMEE GEFSEAREDM AALEKDYEEV GVDS

UniProtKB: Tubulin alpha chain

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Macromolecule #2: Tubulin beta chain

MacromoleculeName: Tubulin beta chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Bos taurus (domestic cattle)
Molecular weightTheoretical: 47.940945 KDa
Recombinant expressionOrganism: Bos taurus (domestic cattle)
SequenceString: MREIVHIQAG QCGNQIGAKF WEVISDEHGI DPTGSYHGDS DLQLERINVY YNEAAGNKYV PRAILVDLEP GTMDSVRSGP FGQIFRPDN FVFGQSGAGN NWAKGHYTEG AELVDSVLDV VRKESESCDC LQGFQLTHSL GGGTGSGMGT LLISKIREEY P DRIMNTFS ...String:
MREIVHIQAG QCGNQIGAKF WEVISDEHGI DPTGSYHGDS DLQLERINVY YNEAAGNKYV PRAILVDLEP GTMDSVRSGP FGQIFRPDN FVFGQSGAGN NWAKGHYTEG AELVDSVLDV VRKESESCDC LQGFQLTHSL GGGTGSGMGT LLISKIREEY P DRIMNTFS VVPSPKVSDT VVEPYNATLS VHQLVENTDE TYCIDNEALY DICFRTLKLT TPTYGDLNHL VSATMSGVTT CL RFPGQLN ADLRKLAVNM VPFPRLHFFM PGFAPLTSRG SQQYRALTVP ELTQQMFDAK NMMAACDPRH GRYLTVAAVF RGR MSMKEV DEQMLNVQNK NSSYFVEWIP NNVKTAVCDI PPRGLKMSAT FIGNSTAIQE LFKRISEQFT AMFRRKAFLH WYTG EGMDE MEFTEAESNM NDLVSEYQQY QD

UniProtKB: Tubulin beta chain

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Macromolecule #3: Disks large-associated protein 5,Green fluorescent protein

MacromoleculeName: Disks large-associated protein 5,Green fluorescent protein
type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 76.169734 KDa
Recombinant expressionOrganism: Bacteria (eubacteria)
SequenceString: MGSSHHHHHH SQDPNSDYDI PTTENLYFQG AAAMPTSLRM TRSATQAAKQ VPRTVSSTTA RKPVTRAANE NEPEGKVPSK GRPAKNVET KPDKGISCKV DSEENTLNSQ TNATSGMNPD GVLSKMENLP EINTAKIKGK NSFAPKDFMF QPLDGLKTYQ V TPMTPRSA ...String:
MGSSHHHHHH SQDPNSDYDI PTTENLYFQG AAAMPTSLRM TRSATQAAKQ VPRTVSSTTA RKPVTRAANE NEPEGKVPSK GRPAKNVET KPDKGISCKV DSEENTLNSQ TNATSGMNPD GVLSKMENLP EINTAKIKGK NSFAPKDFMF QPLDGLKTYQ V TPMTPRSA NAFLTPSYTW TPLKTEVDES QATKEILAQK CKTYSTKTIQ QDSNKLPCPL GPLTVWHEEH VLNKNEATTK NL NGLPIKE VPSLERNEGR IAQPHHGVPY FRNILQSETE KLTSHCFEWD RKLELDIPDD AKDLIRTAVG QTRLLMKERF KQF EGLVDD CEYKRGIKET TCTDLDGFWD MVSFQIEDVI HKFNNLIKLE ESGWQVNNNM NHNMNKNVFR KKVVSGIASK PKQD DAGRI AARNRLAAIK NAMRERIRQE ECAETAVSVI PKEVDKIVFD AGFFRVESPL EGMVSKGEEL FTGVVPILVE LDGDV NGHK FSVSGEGEGD ATYGKLTLKF ICTTGKLPVP WPTLVTTLTY GVQCFSRYPD HMKQHDFFKS AMPEGYVQER TIFFKD DGN YKTRAEVKFE GDTLVNRIEL KGIDFKEDGN ILGHKLEYNY NSHNVYIMAD KQKNGIKVNF KIRHNIEDGS VQLADHY QQ NTPIGDGPVL LPDNHYLSTQ SALSKDPNEK RDH

UniProtKB: Disks large-associated protein 5, Green fluorescent protein

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.4
GridMaterial: COPPER
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 1.2 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: NONE
Startup modelType of model: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.54 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 248567
Initial angle assignmentType: NOT APPLICABLE
Final angle assignmentType: NOT APPLICABLE
FSC plot (resolution estimation)

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