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- EMDB-13149: Mammalian orthoreovirus T3SA- in complex with the neural receptor NgR1 -
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Open data
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Basic information
Entry | ![]() | |||||||||
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Title | Mammalian orthoreovirus T3SA- in complex with the neural receptor NgR1 | |||||||||
![]() | cryoEM reconstruction of T3D orthoreovirus in complex with its neural receptor NgR1 | |||||||||
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![]() | Reovirus / NgR1 / complex / receptor / VIRUS | |||||||||
Function / homology | ![]() neuronal signal transduction / ganglioside GM1 binding / icosahedral viral capsid / chondroitin sulfate binding / neuregulin receptor activity / ganglioside GT1b binding / negative regulation of axon regeneration / host cell surface binding / viral inner capsid / symbiont-mediated suppression of host PKR/eIFalpha signaling ...neuronal signal transduction / ganglioside GM1 binding / icosahedral viral capsid / chondroitin sulfate binding / neuregulin receptor activity / ganglioside GT1b binding / negative regulation of axon regeneration / host cell surface binding / viral inner capsid / symbiont-mediated suppression of host PKR/eIFalpha signaling / viral outer capsid / negative regulation of axon extension / Axonal growth inhibition (RHOA activation) / corpus callosum development / permeabilization of host organelle membrane involved in viral entry into host cell / symbiont entry into host cell via permeabilization of inner membrane / protein serine/threonine kinase inhibitor activity / host cell endoplasmic reticulum / positive regulation of Rho protein signal transduction / host cell mitochondrion / 7-methylguanosine mRNA capping / axonal growth cone / viral life cycle / axonogenesis / positive regulation of GTPase activity / dendritic shaft / presynapse / mRNA guanylyltransferase activity / negative regulation of neuron projection development / regulation of translation / signaling receptor activity / heparin binding / mRNA guanylyltransferase / mRNA (guanine-N7)-methyltransferase / perikaryon / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / host cell cytoplasm / RNA helicase activity / cell surface receptor signaling pathway / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / RNA helicase / neuron projection / membrane raft / external side of plasma membrane / virus-mediated perturbation of host defense response / neuronal cell body / glutamatergic synapse / host cell nucleus / protein-containing complex binding / GTP binding / host cell plasma membrane / structural molecule activity / cell surface / endoplasmic reticulum / ATP hydrolysis activity / RNA binding / extracellular exosome / ATP binding / membrane / metal ion binding / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 8.9 Å | |||||||||
![]() | Strebl M / Sutherland DM / Yu X / Hu L / Wang Z / Prasad BVV / Stehle T / Dermody TS | |||||||||
Funding support | ![]()
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![]() | ![]() Title: NgR1 binding to reovirus reveals an unusual bivalent interaction and a new viral attachment protein. Authors: Danica M Sutherland / Michael Strebl / Melanie Koehler / Olivia L Welsh / Xinzhe Yu / Liya Hu / Rita Dos Santos Natividade / Jonathan J Knowlton / Gwen M Taylor / Rodolfo A Moreno / Patrick ...Authors: Danica M Sutherland / Michael Strebl / Melanie Koehler / Olivia L Welsh / Xinzhe Yu / Liya Hu / Rita Dos Santos Natividade / Jonathan J Knowlton / Gwen M Taylor / Rodolfo A Moreno / Patrick Wörz / Zachery R Lonergan / Pavithra Aravamudhan / Camila Guzman-Cardozo / Sukhleen Kour / Udai Bhan Pandey / David Alsteens / Zhao Wang / B V Venkataram Prasad / Thilo Stehle / Terence S Dermody / ![]() ![]() ![]() Abstract: Nogo-66 receptor 1 (NgR1) binds a variety of structurally dissimilar ligands in the adult central nervous system to inhibit axon extension. Disruption of ligand binding to NgR1 and subsequent ...Nogo-66 receptor 1 (NgR1) binds a variety of structurally dissimilar ligands in the adult central nervous system to inhibit axon extension. Disruption of ligand binding to NgR1 and subsequent signaling can improve neuron outgrowth, making NgR1 an important therapeutic target for diverse neurological conditions such as spinal crush injuries and Alzheimer's disease. Human NgR1 serves as a receptor for mammalian orthoreovirus (reovirus), but the mechanism of virus-receptor engagement is unknown. To elucidate how NgR1 mediates cell binding and entry of reovirus, we defined the affinity of interaction between virus and receptor, determined the structure of the virus-receptor complex, and identified residues in the receptor required for virus binding and infection. These studies revealed that central NgR1 surfaces form a bridge between two copies of viral capsid protein σ3, establishing that σ3 serves as a receptor ligand for reovirus. This unusual binding interface produces high-avidity interactions between virus and receptor to prime early entry steps. These studies refine models of reovirus cell-attachment and highlight the evolution of viruses to engage multiple receptors using distinct capsid components. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 3.1 GB | ![]() | |
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Header (meta data) | ![]() ![]() | 25.6 KB 25.6 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 33.9 KB | Display | ![]() |
Images | ![]() | 208.2 KB | ||
Others | ![]() ![]() | 3.1 GB 3.1 GB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 817 KB | Display | ![]() |
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Full document | ![]() | 816.6 KB | Display | |
Data in XML | ![]() | 40.3 KB | Display | |
Data in CIF | ![]() | 54.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
File | ![]() | ||||||||||||||||||||
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Annotation | cryoEM reconstruction of T3D orthoreovirus in complex with its neural receptor NgR1 | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.74 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: odd half map
File | emd_13149_half_map_1.map | ||||||||||||
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Annotation | odd half map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: even hald map
File | emd_13149_half_map_2.map | ||||||||||||
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Annotation | even hald map | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Mammalian orthoreovirus T3SA- in complex with the neural receptor NgR1
Entire | Name: Mammalian orthoreovirus T3SA- in complex with the neural receptor NgR1 |
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Components |
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-Supramolecule #1: Mammalian orthoreovirus T3SA- in complex with the neural receptor NgR1
Supramolecule | Name: Mammalian orthoreovirus T3SA- in complex with the neural receptor NgR1 type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: Mammalian orthoreovirus T3SA- in complex
Supramolecule | Name: Mammalian orthoreovirus T3SA- in complex / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#5 |
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Source (natural) | Organism: ![]() |
-Supramolecule #3: Nogo receptor 1
Supramolecule | Name: Nogo receptor 1 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #6 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: T3SA- reovirus inner capsid protein lambda1
Macromolecule | Name: T3SA- reovirus inner capsid protein lambda1 / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MKRIPRKTKG KSSGKGNDST ERADDGSSQL RDKQNNKAGP ATTEPGTSNR EQYKARPGIA SVQRATESAE MPMKNNDEGT PDKKGNTKGD LVNEHSEAKD EADEATKKQA KDTDKSKAQV TYSDTGINNA NELSRSGNVD NEGGSNQKPM STRIAEATSA IVSKHPARVG ...String: MKRIPRKTKG KSSGKGNDST ERADDGSSQL RDKQNNKAGP ATTEPGTSNR EQYKARPGIA SVQRATESAE MPMKNNDEGT PDKKGNTKGD LVNEHSEAKD EADEATKKQA KDTDKSKAQV TYSDTGINNA NELSRSGNVD NEGGSNQKPM STRIAEATSA IVSKHPARVG LPPTASSGHG YQCHVCSAVL FSPLDLDAHV ASHGLHGNMT LTSSDIQRHI TEFISSWQNH PIVQVSADVE NKKTAQLLHA DTPRLVTWDA GLCTSFKIVP IVPAQVPQDV LAYTFFTSSY AIQSPFPEAA VSRIVVHTRW ASNVDFDRDS SVIMAPPTEN NIHLFKQLLN TETLSVRGAN PLMFRANVLH MLLEFVLDNL YLNRHTGFSQ DHTPFTEGAN LRSLPGPDAE KWYSIMYPTR MGTPNVSKIC NFVASCVRNR VGRFDRAQMM NGAMSEWVDV FETSDALTVS IRGRWMARLA RMNINPTEIE WALTECAQGY VTVTSPYAPI VNRLMPYRIS NAERQISQII RIMNIGNNAT VIQPVLQDIS VLLQRISPLQ IDPTIISNTM STVSESTTQT LSPASSILGK LRPSNSDFSS FRVALAGWLY NGVVTTVIDD SSYPKDGGSV TSLENLWDFF ILALALPLTT DPCAPVKAFM TLANMMVGFE TIPMDNQIYT QSRRASAFST PHTWPRCFMN IQLISPIDAP ILRQWAEIIH RYWPNPSQIR YGAPNVFGSA NLFTPPEVLL LPIDHQPANV TTPTLDFTNE LTNWRARVCE LMKNLVDNQR YQPGWTQSLV SSMRGTLDKL KLIKSMTPMY LQQLAPVELA VIAPMLPFPP FQVPYVRLDR DRVPTMVGVT RQSRDTITQP ALSLSTTNTT VGVPLALDAR AITVALLSGK YPPDLVTNVW YADAIYPMYA DTEVFSNLQR DMITCEAVQT LVTLVAQISE TQYPVDRYLD WIPSLRASAA TAATFAEWVN TSMKTAFDLS DMLLEPLLSG DPRMTQLAIQ YQQYNGRTFN IIPEMPGSVI ADCVQLTAEV FNHEYNLFGI ARGDIIIGRV QSTHLWSPLA PPPDLVFDRD TPGVHIFGRD CRISFGMNGA APMIRDETGL MVPFEGNWIF PLALWQMNTR YFNQQFDAWI KTGELRIRIE MGAYPYMLHY YDPRQYANAW NLTSAWLEEI TPTSIPSVPF MVPISSDHDI SSAPAVQYII STEYNDRSLF CTNSSSPQTI AGPDKHIPVE RYNILTNPDA PPTQIQLPEV VDLYNVVTRY AYETPPITAV VMGVP UniProtKB: Inner capsid protein lambda-1 |
-Macromolecule #2: T3SA- reovirus inner capsid protein sigma2
Macromolecule | Name: T3SA- reovirus inner capsid protein sigma2 / type: protein_or_peptide / ID: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MARAAFLFKT VGFGGLQNVP INDELSSHLL RAGNSPWQLT QFLDWISLGR GLATSALVPT AGSRYYQMSC LLSGTLQIPF RPNHRWGDIR FLRLVWSAPT LDGLVVAPPQ VLAQPALQAQ ADRVYDCDDY PFLARDPRFK HRVYQQLSAV TLLNLTGFGP ISYVRVDEDM ...String: MARAAFLFKT VGFGGLQNVP INDELSSHLL RAGNSPWQLT QFLDWISLGR GLATSALVPT AGSRYYQMSC LLSGTLQIPF RPNHRWGDIR FLRLVWSAPT LDGLVVAPPQ VLAQPALQAQ ADRVYDCDDY PFLARDPRFK HRVYQQLSAV TLLNLTGFGP ISYVRVDEDM WSGDVNQLLM NYFGHTFAEI AYTLCQASAN RPWEYDGTYA RMTQIVLSLF WLSYVGVIHQ QNTYRTFYFQ CNRRGDAAEV WILSCSLNHS AQIRPGNRSL FVMPTSPDWN MDVNLILSST LTGCLCSGSQ LPLIDNNSVP AVSRNIHGWT GRAGNQLHGF QVRRMVTEFC DRLRRDGVMT QAQQNQVEAL ADQTQQFKRD KLETWAREDD QYNQAHPNST MFRTKPFTNA QWGRGNTGAT SAAIAALI UniProtKB: Inner capsid protein sigma-2 |
-Macromolecule #3: T3SA- reovirus outer capsid protein lambda2
Macromolecule | Name: T3SA- reovirus outer capsid protein lambda2 / type: protein_or_peptide / ID: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MANVWGVRLA DSLSSPTIET RTRQYTLHDL CSDLDANPGR EPWKPLRNQR TNNIVAVQLF RPLQGLVLDT QLYGFPGAFD DWERFMREKL RVLKYEVLRI YPISNYSNEH VNVFVANALV GAFLSNQAFY DLLPLLIIND TMIGDLLGTG ASLSQFFQSH GDVLEVAAGR ...String: MANVWGVRLA DSLSSPTIET RTRQYTLHDL CSDLDANPGR EPWKPLRNQR TNNIVAVQLF RPLQGLVLDT QLYGFPGAFD DWERFMREKL RVLKYEVLRI YPISNYSNEH VNVFVANALV GAFLSNQAFY DLLPLLIIND TMIGDLLGTG ASLSQFFQSH GDVLEVAAGR KYLQMENYSN DDDDPPLFAK DLSDYAKAFY SDTYEVLDRF FWTHDSSAGV LVHYDKPTNG HHYLLGTLTQ MVSAPPYIIN ATDAMLLESC LEQFSANVRA RPAQPVTRLD QCYHLRWGAQ YVGEDSLTYR LGVLSLLATN GYQLARPIPR QLTNRWLSSF VSQIMSDGVN ETPLWPQERY VQIAYDSPSV VDGATQYGYV RKNQLRLGMR ISALQSLSDT PSPVQWLPQY TIDQAAMDEG DLMVSRLTQL PLRPDYGNIW VGDALSYYVD YNRSHRVVLS SELPQLPDTY FDGDEQYGRS LFSLARKIGD RSLVKDTAVL KHAYQAIDPN TGKEYLRSRQ SVAYFGASAG HSGADQPLVI EPWIQGKISG VPPPSSVRQF GYDVARGAIV DLARPFPSGD YQFVYSDVDQ VVDGHDDLSI SSGLVESLLS SCMHATAPGG SFVVKINFPT RPVWHYIEQK ILPNITSYML IKPFVTNNVE LFFVAFGVHQ HSSLTWTSGV YFFLVDHFYR YETLSTISRQ LPSFGYVDDG SSVTGIETIS IENPGFSNMT QAARIGISGL CANVGNARKS IAIYESHGAR VLTITSRRSP ASARRKSRLR YLPLIDPRSL EVQARTILPA DPVLFENVSG ASPHVCLTMM YNFEVSSAVY DGDVVLDLGT GPEAKILELI PATSPVTCVD IRPTAQPSGC WNVRTTFLEL DYLSDGWITG VRGDIVTCML SLGAAAAGKS MTFDAAFQQL IKVLSKSTAN VVLVQVNCPT DVVRSIKGYL EIDSTNKRYR FPKFGRDEPY SDMDALEKIC RTAWPNCSIT WVPLSYDLRW TRLALLESTT LSSASIRIAE LMYKYMPIMR IDIHGLPMEK RGNFIVGQNC SLVIPGFNAQ DVFNCYFNSA LAFSTEDVNA AMIPQVSAQF DATKGEWTLD MVFSDAGIYT MQALVGSNAN PVSLGSFVVD SPDVDITDAW PAQLDFTIAG TDVDITVNPY YRLMTFVRID GQWQIANPDK FQFFSSASGT LVMNVKLDIA DKYLLYYIRD VQSRDVGFYI QHPLQLLNTI TLPTNEDLFL SAPDMREWAV KESGNTICIL NSQGFVLPQD WDVLTDTISW SPSIPTYIVP PGDYTLTPL UniProtKB: Outer capsid protein lambda-2 |
-Macromolecule #4: T3SA- reovirus outer capsid protein mu1
Macromolecule | Name: T3SA- reovirus outer capsid protein mu1 / type: protein_or_peptide / ID: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MGNASSIVQT INVTGDGNVF KPSAETSSTA VPSLSLSPGM LNPGGVPWIA VGDETSVTSP GALRRMTSKD IPETAIINTD NSSGAVPSES ALVPYIDEPL VVVTEHAITN FTKAEMALEF NREFLDKMRV LSVSPKYSDL LTYVDCYVGV SARQALNNFQ KQVPVITPTR ...String: MGNASSIVQT INVTGDGNVF KPSAETSSTA VPSLSLSPGM LNPGGVPWIA VGDETSVTSP GALRRMTSKD IPETAIINTD NSSGAVPSES ALVPYIDEPL VVVTEHAITN FTKAEMALEF NREFLDKMRV LSVSPKYSDL LTYVDCYVGV SARQALNNFQ KQVPVITPTR QTMYVDSIQA ALKALEKWEI DLRVAQTLLP TNVPIGEVSC PMQSVVKLLD DQLPDDSLIR RYPKEAAVAL AKRNGGIQWM DVSEGTVMNE AVNAVAASAL APSASAPPLE EKSKLTEQAM DLVTAAEPEI IASLAPVPAP VFAIPPKPAD YNVRTLRIDE ATWLRMIPKS MNTPFQIQVT DNTGTNWHLN LRGGTRVVNL DQIAPMRFVL DLGGKSYKET SWDPNGKKVG FIVFQSKIPF ELWTAASQIG QATVVNYVQL YAEDSSFTAQ SIIATTSLAY NYEPEQLNKT DPEMNYYLLA TFIDSAAITP TNMTQPDVWD ALLTMSPLSA GEVTVKGAVV SEVVPADLIG SYTPESLNAS LPNDAARCMI DRASKIAEAI KIDDDAGPDE YSPNSVPIQG QLAISQLETG YGVRIFNPKG ILSKIASRAM QAFIGDPSTI ITQAAPVLSD KNNWIALAQG VKTSLRTKSL SAGVKTAVSK LSSSESIQNW TQGFLDKVSA HFPAPKPDCP TSGDSGESSN RRVKRDSYAG VVKRGYTR UniProtKB: Outer capsid protein mu-1 |
-Macromolecule #5: T3SA- reovirus outer capsid protein sigma3
Macromolecule | Name: T3SA- reovirus outer capsid protein sigma3 / type: protein_or_peptide / ID: 5 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MEVCLPNGHQ VVDLINNAFE GRVSIYSAQE GWDKTISAQP DMMVCGGAVV CMHCLGVVGS LQRKLKHLPH HRCNQQIRHQ DYVDVQFADR VTAHWKRGML SFVAQMHEMM NDVSPDDLDR VRTEGGSLVE LNWLQVDPNS MFRSIHSSWT DPLQVVDDLD TKLDQYWTAL ...String: MEVCLPNGHQ VVDLINNAFE GRVSIYSAQE GWDKTISAQP DMMVCGGAVV CMHCLGVVGS LQRKLKHLPH HRCNQQIRHQ DYVDVQFADR VTAHWKRGML SFVAQMHEMM NDVSPDDLDR VRTEGGSLVE LNWLQVDPNS MFRSIHSSWT DPLQVVDDLD TKLDQYWTAL NLMIDSSDLI PNFMMRDPSH AFNGVKLGGD ARQTQFSRTF DSRSSLEWGV MVYDYSELEH DPSKGRAYRK ELVTPARDFG HFGLSHYSRA TTPILGKMPA VFSGMLTGNC KMYPFIKGTA KLKTVRKLVE AVNHAWGVEK IRYALGPGGM TGWYNRTMQQ APIVLTPAAL TMFPDTIKFG DLNYPVMIGD PMILG UniProtKB: Outer capsid protein sigma-3 |
-Macromolecule #6: Nogo receptor 1
Macromolecule | Name: Nogo receptor 1 / type: protein_or_peptide / ID: 6 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
Sequence | String: MKRASAGGSR LLAWVLWLQA WQVAAPCPGA CVCYNEPKVT TSCPQQGLQA VPVGIPAASQ RIFLHGNRIS HVPAASFRAC RNLTILWLHS NVLARIDAAA FTGLALLEQL DLSDNAQLRS VDPATFHGLG RLHTLHLDRC GLQELGPGLF RGLAALQYLY LQDNALQALP ...String: MKRASAGGSR LLAWVLWLQA WQVAAPCPGA CVCYNEPKVT TSCPQQGLQA VPVGIPAASQ RIFLHGNRIS HVPAASFRAC RNLTILWLHS NVLARIDAAA FTGLALLEQL DLSDNAQLRS VDPATFHGLG RLHTLHLDRC GLQELGPGLF RGLAALQYLY LQDNALQALP DDTFRDLGNL THLFLHGNRI SSVPERAFRG LHSLDRLLLH QNRVAHVHPH AFRDLGRLMT LYLFANNLSA LPTEALAPLR ALQYLRLNDN PWVCDCRARP LWAWLQKFRG SSSEVPCSLP QRLAGRDLKR LAANDLQGCA HHHHHHH UniProtKB: Reticulon-4 receptor |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 / Component - Name: PBS |
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Grid | Model: Quantifoil R3.5/1 / Material: COPPER / Mesh: 200 / Support film - Material: CARBON / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 90 % / Chamber temperature: 291 K / Instrument: FEI VITROBOT MARK IV / Details: blot for 3.5 seconds before plunging. |
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Electron microscopy
Microscope | JEOL 3200FSC |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 27.5 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 4.1 mm |