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Yorodumi- EMDB-10793: Cryo-EM structure of the Full-length disease type human Huntingtin -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-10793 | |||||||||
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Title | Cryo-EM structure of the Full-length disease type human Huntingtin | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information regulation of cAMP-dependent protein kinase activity / regulation of phosphoprotein phosphatase activity / positive regulation of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity / microtubule-based transport / vocal learning / regulation of CAMKK-AMPK signaling cascade / positive regulation of mitophagy / profilin binding / vesicle transport along microtubule / positive regulation of cilium assembly ...regulation of cAMP-dependent protein kinase activity / regulation of phosphoprotein phosphatase activity / positive regulation of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity / microtubule-based transport / vocal learning / regulation of CAMKK-AMPK signaling cascade / positive regulation of mitophagy / profilin binding / vesicle transport along microtubule / positive regulation of cilium assembly / presynaptic cytosol / retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum / positive regulation of aggrephagy / postsynaptic cytosol / positive regulation of lipophagy / dynein intermediate chain binding / beta-tubulin binding / Golgi organization / establishment of mitotic spindle orientation / dynactin binding / Regulation of MECP2 expression and activity / autophagosome / inclusion body / heat shock protein binding / centriole / negative regulation of extrinsic apoptotic signaling pathway / protein destabilization / cytoplasmic vesicle membrane / kinase binding / p53 binding / late endosome / transmembrane transporter binding / early endosome / positive regulation of apoptotic process / axon / apoptotic process / dendrite / perinuclear region of cytoplasm / Golgi apparatus / endoplasmic reticulum / protein-containing complex / nucleoplasm / identical protein binding / nucleus / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 18.2 Å | |||||||||
Authors | Jung T / Tamo G / Dal Perraro M / Hebert H / Song J | |||||||||
Funding support | Korea, Republic Of, 2 items
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Citation | Journal: Structure / Year: 2020 Title: The Polyglutamine Expansion at the N-Terminal of Huntingtin Protein Modulates the Dynamic Configuration and Phosphorylation of the C-Terminal HEAT Domain. Authors: Taeyang Jung / Baehyun Shin / Giorgio Tamo / Hyeongju Kim / Ravi Vijayvargia / Alexander Leitner / Maria J Marcaida / Juan Astorga-Wells / Roy Jung / Ruedi Aebersold / Matteo Dal Peraro / ...Authors: Taeyang Jung / Baehyun Shin / Giorgio Tamo / Hyeongju Kim / Ravi Vijayvargia / Alexander Leitner / Maria J Marcaida / Juan Astorga-Wells / Roy Jung / Ruedi Aebersold / Matteo Dal Peraro / Hans Hebert / Ihn Sik Seong / Ji-Joon Song / Abstract: The polyQ expansion in huntingtin protein (HTT) is the prime cause of Huntington's disease (HD). The recent cryoelectron microscopy (cryo-EM) structure of HTT-HAP40 complex provided the structural ...The polyQ expansion in huntingtin protein (HTT) is the prime cause of Huntington's disease (HD). The recent cryoelectron microscopy (cryo-EM) structure of HTT-HAP40 complex provided the structural information on its HEAT-repeat domains. Here, we present analyses of the impact of polyQ length on the structure and function of HTT via an integrative structural and biochemical approach. The cryo-EM analysis of normal (Q23) and disease (Q78) type HTTs shows that the structures of apo HTTs significantly differ from the structure of HTT in a HAP40 complex and that the polyQ expansion induces global structural changes in the relative movements among the HTT domains. In addition, we show that the polyQ expansion alters the phosphorylation pattern across HTT and that Ser2116 phosphorylation in turn affects the global structure and function of HTT. These results provide a molecular basis for the effect of the polyQ segment on HTT structure and activity, which may be important for HTT pathology. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_10793.map.gz | 19.1 MB | EMDB map data format | |
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Header (meta data) | emd-10793-v30.xml emd-10793.xml | 18.9 KB 18.9 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_10793_fsc.xml | 8.6 KB | Display | FSC data file |
Images | emd_10793.png | 41 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-10793 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-10793 | HTTPS FTP |
-Related structure data
Related structure data | 6yejMC 4937C 4944C 6rmhC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_10793.map.gz / Format: CCP4 / Size: 52.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.06 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : Full-length human disease-type huntingtin
Entire | Name: Full-length human disease-type huntingtin |
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Components |
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-Supramolecule #1: Full-length human disease-type huntingtin
Supramolecule | Name: Full-length human disease-type huntingtin / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: all Details: A disease type huntingtin with 78 polyglutamine repeat tract |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Experimental: 350 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) / Recombinant cell: Sf9 cell / Recombinant plasmid: pFASTBAC1 |
-Macromolecule #1: Huntingtin
Macromolecule | Name: Huntingtin / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 355.278719 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MATLEKLMKA FESLKSFQQQ QQQQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ QQQQQQQQQ QQQQQQPPPP PPPPPPPQLP QPPPQAQPLL PQPQPPPPPP PPPPGPAVAE EPLHRPKKEL SATKKDRVNH C LTICENIV ...String: MATLEKLMKA FESLKSFQQQ QQQQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ QQQQQQQQQ QQQQQQPPPP PPPPPPPQLP QPPPQAQPLL PQPQPPPPPP PPPPGPAVAE EPLHRPKKEL SATKKDRVNH C LTICENIV AQSVRNSPEF QKLLGIAMEL FLLCSDDAES DVRMVADECL NKVIKALMDS NLPRLQLELY KEIKKNGAPR SL RAALWRF AELAHLVRPQ KCRPYLVNLL PCLTRTSKRP EESVQETLAA AVPKIMASFG NFANDNEIKV LLKAFIANLK SSS PTIRRT AAGSAVSICQ HSRRTQYFYS WLLNVLLGLL VPVEDEHSTL LILGVLLTLR YLVPLLQQQV KDTSLKGSFG VTRK EMEVS PSAEQLVQVY ELTLHHTQHQ DHNVVTGALE LLQQLFRTPP PELLQTLTAV GGIGQLTAAK EESGGRSRSG SIVEL IAGG GSSCSPVLSR KQKGKVLLGE EEALEDDSES RSDVSSSALT ASVKDEISGE LAASSGVSTP GSAGHDIITE QPRSQH TLQ ADSVDLASCD LTSSATDGDE EDILSHSSSQ VSAVPSDPAM DLNDGTQASS PISDSSQTTT EGPDSAVTPS DSSEIVL DG TDNQYLGLQI GQPQDEDEEA TGILPDEASE AFRNSSMALQ QAHLLKNMSH CRQPSDSSVD KFVLRDEATE PGDQENKP C RIKGDIGQST DDDSAPLVHC VRLLSASFLL TGGKNVLVPD RDVRVSVKAL ALSCVGAAVA LHPESFFSKL YKVPLDTTE YPEEQYVSDI LNYIDHGDPQ VRGATAILCG TLICSILSRS RFHVGDWMGT IRTLTGNTFS LADCIPLLRK TLKDESSVTC KLACTAVRN CVMSLCSSSY SELGLQLIID VLTLRNSSYW LVRTELLETL AEIDFRLVSF LEAKAENLHR GAHHYTGLLK L QERVLNNV VIHLLGDEDP RVRHVAAASL IRLVPKLFYK CDQGQADPVV AVARDQSSVY LKLLMHETQP PSHFSVSTIT RI YRGYNLL PSITDVTMEN NLSRVIAAVS HELITSTTRA LTFGCCEALC LLSTAFPVCI WSLGWHCGVP PLSASDESRK SCT VGMATM ILTLLSSAWF PLDLSAHQDA LILAGNLLAA SAPKSLRSSW ASEEEANPAA TKQEEVWPAL GDRALVPMVE QLFS HLLKV INICAHVLDD VAPGPAIKAA LPSLTNPPSL SPIRRKGKEK EPGEQASVPL SPKKGSEASA ASRQSDTSGP VTTSK SSSL GSFYHLPSYL RLHDVLKATH ANYKVTLDLQ NSTEKFGGFL RSALDVLSQI LELATLQDIG KCVEEILGYL KSCFSR EPM MATVCVQQLL KTLFGTNLAS QFDGLSSNPS KSQGRAQRLG SSSVRPGLYH YCFMAPYTHF TQALADASLR NMVQAEQ EN DTSGWFDVLQ KVSTQLKTNL TSVTKNRADK NAIHNHIRLF EPLVIKALKQ YTTTTCVQLQ KQVLDLLAQL VQLRVNYC L LDSDQVFIGF VLKQFEYIEV GQFRESEAII PNIFFFLVLL SYERYHSKQI IGIPKIIQLC DGIMASGRKA VTHAIPALQ PIVHDLFVLR GTNKADAGKE LETQKEVVVS MLLRLIQYHQ VLEMFILVLQ QCHKENEDKW KRLSRQIADI ILPMLAKQQM HIDSHEALG VLNTLFEILA PSSLRPVDML LRSMFVTPNT MASVSTVQLW ISGILAILRV LISQSTEDIV LSRIQELSFS P YLISCTVI NRLRDGDSTS TLEEHSEGKQ IKNLPEETFS RFLLQLVGIL LEDIVTKQLK VEMSEQQHTF YCQELGTLLM CL IHIFKSG MFRRITAAAT RLFRSDGCGG SFYTLDSLNL RARSMITTHP ALVLLWCQIL LLVNHTDYRW WAEVQQTPKR HSL SSTKLL SPQMSGEEED SDLAAKLGMC NREIVRRGAL ILFCDYVCQN LHDSEHLTWL IVNHIQDLIS LSHEPPVQDF ISAV HRNSA ASGLFIQAIQ SRCENLSTPT MLKKTLQCLE GIHLSQSGAV LTLYVDRLLC TPFRVLARMV DILACRRVEM LLAAN LQSS MAQLPMEELN RIQEYLQSSG LAQRHQRLYS LLDRFRLSTM QDSLSPSPPV SSHPLDGDGH VSLETVSPDK DWYVHL VKS QCWTRSDSAL LEGAELVNRI PAEDMNAFMM NSEFNLSLLA PCLSLGMSEI SGGQKSALFE AAREVTLARV SGTVQQL PA VHHVFQPELP AEPAAYWSKL NDLFGDAALY QSLPTLARAL AQYLVVVSKL PSHLHLPPEK EKDIVKFVVA TLEALSWH L IHEQIPLSLD LQAGLDCCCL ALQLPGLWSV VSSTEFVTHA CSLIHCVHFI LEAVAVQPGE QLLSPERRTN TPKAISEEE EEVDPNTQNP KYITAACEMV AEMVESLQSV LALGHKRNSG VPAFLTPLLR NIIISLARLP LVNSYTRVPP LVWKLGWSPK PGGDFGTAF PEIPVEFLQE KEVFKEFIYR INTLGWTSRT QFEETWATLL GVLVTQPLVM EQEESPPEED TERTQINVLA V QAITSLVL SAMTVPVAGN PAVSCLEQQP RNKPLKALDT RFGRKLSIIR GIVEQEIQAM VSKRENIATH HLYQAWDPVP SL SPATTGA LISHEKLLLQ INPERELGSM SYKLGQVSIH SVWLGNSITP LREEEWDEEE EEEADAPAPS SPPTSPVNSR KHR AGVDIH SCSQFLLELY SRWILPSSSA RRTPAILISE VVRSLLVVSD LFTERNQFEL MYVTLTELRR VHPSEDEILA QYLV PATCK AAAVLGMDKA VAEPVSRLLE STLRSSHLPS RVGALHGVLY VLECDLLDDT AKQLIPVISD YLLSNLKGIA HCVNI HSQQ HVLVMCATAF YLIENYPLDV GPEFSASIIQ MCGVMLSGSE ESTPSIIYHC ALRGLERLLL SEQLSRLDAE SLVKLS VDR VNVHSPHRAM AALGLMLTCM YTGKEKVSPG RTSDPNPAAP DSESVIVAME RVSVLFDRIR KGFPCEARVV ARILPQF LD DFFPPQDIMN KVIGEFLSNQ QPYPQFMATV VYKVFQTLHS TGQSSMVRDW VMLSLSNFTQ RAPVAMATWS LSCFFVSA S TSPWVAAILP HVISRMGKLE QVDVNLFCLV ATDFYRHQIE EELDRRAFQS VLEVVAAPGS PYHRLLTCLR NVHKVTTC |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.08 mg/mL | |||||||||
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Buffer | pH: 7.5 Component:
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Grid | Model: Quantifoil R2/2 / Material: COPPER / Mesh: 300 / Support film - Material: GRAPHENE OXIDE / Support film - topology: CONTINUOUS / Pretreatment - Type: GLOW DISCHARGE | |||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 288 K / Instrument: FEI VITROBOT MARK II / Details: 30 seconds incubation 8 seconds blotting. | |||||||||
Details | HTT was mixed with final 0.05% of Octyl glucoside. |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Calibrated magnification: 47170 / Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / Nominal defocus max: 0.4 µm / Nominal defocus min: 0.4 µm |
Specialist optics | Phase plate: VOLTA PHASE PLATE / Energy filter - Slit width: 20 eV |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Digitization - Frames/image: 1-24 / Number real images: 1500 / Average exposure time: 6.0 sec. / Average electron dose: 33.6 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |