+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-0836 | |||||||||
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Title | Structure of SMG1 | |||||||||
Map data | ||||||||||
Sample |
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Keywords | SMG1 / Cryo-EM / Nonsense-mediated mRNA decay / TRANSFERASE | |||||||||
Function / homology | Function and homology information diacylglycerol-dependent serine/threonine kinase activity / chromatoid body / regulation of telomere maintenance / nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / telomeric DNA binding / phosphatidylinositol phosphate biosynthetic process / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / mRNA export from nucleus / peptidyl-serine phosphorylation / protein autophosphorylation ...diacylglycerol-dependent serine/threonine kinase activity / chromatoid body / regulation of telomere maintenance / nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / telomeric DNA binding / phosphatidylinositol phosphate biosynthetic process / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / mRNA export from nucleus / peptidyl-serine phosphorylation / protein autophosphorylation / non-specific serine/threonine protein kinase / protein kinase activity / DNA repair / protein serine kinase activity / protein serine/threonine kinase activity / DNA damage response / RNA binding / nucleoplasm / ATP binding / nucleus / metal ion binding / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.63 Å | |||||||||
Authors | Xu Y / Qi Y | |||||||||
Citation | Journal: Cell Res / Year: 2019 Title: Cryo-EM structure of SMG1-SMG8-SMG9 complex. Authors: Li Zhu / Liang Li / Yilun Qi / Zishuo Yu / Yanhui Xu / Abstract: Nonsense-mediated mRNA decay (NMD) targets premature stop codon (PTC)-containing mRNAs for rapid degradation, and is essential for mammalian embryonic development, brain development and modulation of ...Nonsense-mediated mRNA decay (NMD) targets premature stop codon (PTC)-containing mRNAs for rapid degradation, and is essential for mammalian embryonic development, brain development and modulation of the stress response. The key event in NMD is the SMG1-mediated phosphorylation of an RNA helicase UPF1 and SMG1 kinase activity is inhibited by SMG8 and SMG9 in an unknown mechanism. Here, we determined the cryo-EM structures of human SMG1 at 3.6 Å resolution and the SMG1-SMG8-SMG9 complex at 3.4 Å resolution, respectively. SMG8 has a C-terminal kinase inhibitory domain (KID), which covers the catalytic pocket and inhibits the kinase activity of SMG1. Structural analyses suggest that GTP hydrolysis of SMG9 would lead to a dramatic conformational change of SMG8-SMG9 and the KID would move away from the inhibitory position to restore SMG1 kinase activity. Thus, our structural and biochemical analyses provide a mechanistic understanding of SMG1-SMG8-SMG9 complex assembly and the regulatory mechanism of SMG1 kinase activity. | |||||||||
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_0836.map.gz | 106.5 MB | EMDB map data format | |
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Header (meta data) | emd-0836-v30.xml emd-0836.xml | 11.7 KB 11.7 KB | Display Display | EMDB header |
Images | emd_0836.png | 50.6 KB | ||
Filedesc metadata | emd-0836.cif.gz | 7 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-0836 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-0836 | HTTPS FTP |
-Validation report
Summary document | emd_0836_validation.pdf.gz | 372.5 KB | Display | EMDB validaton report |
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Full document | emd_0836_full_validation.pdf.gz | 372 KB | Display | |
Data in XML | emd_0836_validation.xml.gz | 6.9 KB | Display | |
Data in CIF | emd_0836_validation.cif.gz | 7.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0836 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0836 | HTTPS FTP |
-Related structure data
Related structure data | 6l53MC 0837C 6l54C M: atomic model generated by this map C: citing same article (ref.) |
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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_0836.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.04 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 : SMG1
Entire | Name: SMG1 |
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Components |
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-Supramolecule #1: SMG1
Supramolecule | Name: SMG1 / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Serine/threonine-protein kinase SMG1
Macromolecule | Name: Serine/threonine-protein kinase SMG1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: non-specific serine/threonine protein kinase |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 410.966969 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MSRRAPGSRL SSGGGGGGTK YPRSWNDWQP RTDSASADPD NLKYSSSRDR GGSSSYGLQP SNSAVVSRQR HDDTRVHADI QNDEKGGYS VNGGSGENTY GRKSLGQELR VNNVTSPEFT SVQHGSRALA TKDMRKSQER SMSYSDESRL SNLLRRITRE D DRDRRLAT ...String: MSRRAPGSRL SSGGGGGGTK YPRSWNDWQP RTDSASADPD NLKYSSSRDR GGSSSYGLQP SNSAVVSRQR HDDTRVHADI QNDEKGGYS VNGGSGENTY GRKSLGQELR VNNVTSPEFT SVQHGSRALA TKDMRKSQER SMSYSDESRL SNLLRRITRE D DRDRRLAT VKQLKEFIQQ PENKLVLVKQ LDNILAAVHD VLNESSKLLQ ELRQEGACCL GLLCASLSYE AEKIFKWIFS KF SSSAKDE VKLLYLCATY KALETVGEKK AFSSVMQLVM TSLQSILENV DTPELLCKCV KCILLVARCY PHIFSTNFRD TVD ILVGWH IDHTQKPSLT QQVSGWLQSL EPFWVADLAF STTLLGQFLE DMEAYAEDLS HVASGESVDE DVPPPSVSLP KLAA LLRVF STVVRSIGER FSPIRGPPIT EAYVTDVLYR VMRCVTAANQ VFFSEAVLTA ANECVGVLLG SLDPSMTIHC DMVIT YGLD QLENCQTCGT DYIISVLNLL TLIVEQINTK LPSSFVEKLF IPSSKLLFLR YHKEKEVVAV AHAVYQAVLS LKNIPV LET AYKLILGEMT CALNNLLHSL QLPEACSEIK HEAFKNHVFN VDNAKFVVIF DLSALTTIGN AKNSLIGMWA LSPTVFA LL SKNLMIVHSD LAVHFPAIQY AVLYTLYSHC TRHDHFISSS LSSSSPSLFD GAVISTVTTA TKKHFSIILN LLGILLKK D NLNQDTRKLL MTWALEAAVL MKKSETYAPL FSLPSFHKFC KGLLANTLVE DVNICLQACS SLHALSSSLP DDLLQRCVD VCRVQLVHSG TRIRQAFGKL LKSIPLDVVL SNNNHTEIQE ISLALRSHMS KAPSNTFHPQ DFSDVISFIL YGNSHRTGKD NWLERLFYS CQRLDKRDQS TIPRNLLKTD AVLWQWAIWE AAQFTVLSKL RTPLGRAQDT FQTIEGIIRS LAAHTLNPDQ D VSQWTTAD NDEGHGNNQL RLVLLLQYLE NLEKLMYNAY EGCANALTSP PKVIRTFFYT NRQTCQDWLT RIRLSIMRVG LL AGQPAVT VRHGFDLLTE MKTTSLSQGN ELEVTIMMVV EALCELHCPE AIQGIAVWSS SIVGKNLLWI NSVAQQAEGR FEK ASVEYQ EHLCAMTGVD CCISSFDKSV LTLANAGRNS ASPKHSLNGE SRKTVLSKPT DSSPEVINYL GNKACECYIS IADW AAVQE WQNAIHDLKK STSSTSLNLK ADFNYIKSLS SFESGKFVEC TEQLELLPGE NINLLAGGSK EKIDMKKLLP NMLSP DPRE LQKSIEVQLL RSSVCLATAL NPIEQDQKWQ SITENVVKYL KQTSRIAIGP LRLSTLTVSQ SLPVLSTLQL YCSSAL ENT VSNRLSTEDC LIPLFSEALR SCKQHDVRPW MQALRYTMYQ NQLLEKIKEQ TVPIRSHLME LGLTAAKFAR KRGNVSL AT RLLAQCSEVQ LGKTTTAQDL VQHFKKLSTQ GQVDEKWGPE LDIEKTKLLY TAGQSTHAME MLSSCAISFC KSVKAEYA V AKSILTLAKW IQAEWKEISG QLKQVYRAQH QQNFTGLSTL SKNILTLIEL PSVNTMEEEY PRIESESTVH IGVGEPDFI LGQLYHLSSV QAPEVAKSWA ALASWAYRWG RKVVDNASQG EGVRLLPREK SEVQNLLPDT ITEEEKERIY GILGQAVCRP AGIQDEDIT LQITESEDNE EDDMVDVIWR QLISSCPWLS ELDESATEGV IKVWRKVVDR IFSLYKLSCS AYFTFLKLNA G QIPLDEDD PRLHLSHRVE QSTDDMIVMA TLRLLRLLVK HAGELRQYLE HGLETTPTAP WRGIIPQLFS RLNHPEVYVR QS ICNLLCR VAQDSPHLIL YPAIVGTISL SSESQASGNK FSTAIPTLLG NIQGEELLVS ECEGGSPPAS QDSNKDEPKS GLN EDQAMM QDCYSKIVDK LSSANPTMVL QVQMLVAELR RVTVLWDELW LGVLLQQHMY VLRRIQQLED EVKRVQNNNT LRKE EKIAI MREKHTALMK PIVFALEHVR SITAAPAETP HEKWFQDNYG DAIENALEKL KTPLNPAKPG SSWIPFKEIM LSLQQ RAQK RASYILRLEE ISPWLAAMTN TEIALPGEVS ARDTVTIHSV GGTITILPTK TKPKKLLFLG SDGKSYPYLF KGLEDL HLD ERIMQFLSIV NTMFATINRQ ETPRFHARHY SVTPLGTRSG LIQWVDGATP LFGLYKRWQQ REAALQAQKA QDSYQTP QN PGIVPRPSEL YYSKIGPALK TVGLSLDVSR RDWPLHVMKA VLEELMEATP PNLLAKELWS SCTTPDEWWR VTQSYARS T AVMSMVGYII GLGDRHLDNV LIDMTTGEVV HIDYNVCFEK GKSLRVPEKV PFRMTQNIET ALGVTGVEGV FRLSCEQVL HIMRRGRETL LTLLEAFVYD PLVDWTAGGE AGFAGAVYGG GGQQAESKQS KREMEREITR SLFSSRVAEI KVNWFKNRDE MLVVLPKLD GSLDEYLSLQ EQLTDVEKLQ GKLLEEIEFL EGAEGVDHPS HTLQHRYSEH TQLQTQQRAV QEAIQVKLNE F EQWITHYQ AAFNNLEATQ LASLLQEIST QMDLGPPSYV PATAFLQNAG QAHLISQCEQ LEGEVGALLQ QRRSVLRGCL EQ LHHYATV ALQYPKAIFQ KHRIEQWKTW MEELICNTTV ERCQELYRKY EMQYAPQPPP TVCQFITATE MTLQRYAADI NSR LIRQVE RLKQEAVTVP VCEDQLKEIE RCIKVFLHEN GEEGSLSLAS VIISALCTLT RRNLMMEGAA SSAGEQLVDL TSRD GAWFL EELCSMSGNV TCLVQLLKQC HLVPQDLDIP NPMEASETVH LANGVYTSLQ ELNSNFRQII FPEALRCLMK GEYTL ESML HELDGLIEQT TDGVPLQTLV ESLQAYLRNA AMGLEEETHA HYIDVARLLH AQYGELIQPR NGSVDETPKM SAGQML LVA FDGMFAQVET AFSLLVEKLN KMEIPIAWRK IDIIREARST QVNFFDDDNH RQVLEEIFFL KRLQTIKEFF RLCGTFS KT LSGSSSLEDQ NTVNGPVQIV NVKTLFRNSC FSEDQMAKPI KAFTADFVRQ LLIGLPNQAL GLTLCSFISA LGVDIIAQ V EAKDFGAESK VSVDDLCKKA VEHNIQIGKF SQLVMNRATV LASSYDTAWK KHDLVRRLET SISSCKTSLQ RVQLHIAMF QWQHEDLLIN RPQAMSVTPP PRSAILTSMK KKLHTLSQIE TSIATVQEKL AALESSIEQR LKWAGGANPA LAPVLQDFEA TIAERRNLV LKESQRASQV TFLCSNIIHF ESLRTRTAEA LNLDAALFEL IKRCQQMCSF ASQFNSSVSE LELRLLQRVD T GLEHPIGS SEWLLSAHKQ LTQDMSTQRA IQTEKEQQIE TVCETIQNLV DNIKTVLTGH NRQLGDVKHL LKAMAKDEEA AL ADGEDVP YENSVRQFLG EYKSWQDNIQ TVLFTLVQAM GQVRSQEHVE MLQEITPTLK ELKTQSQSIY NNLVSFASPL VTD ATNECS SPTSSATYQP SFAAAVRSNT GQKTQPDVMS QNARKLIQKN LATSADTPPS TVPGTGKSVA CSPKKAVRDP KTGK AVQER NSYAVSVWKR VKAKLEGRDV DPNRRMSVAE QVDYVIKEAT NLDNLAQLYE GWTAWV UniProtKB: Serine/threonine-protein kinase SMG1 |
-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 K2 SUMMIT (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: EMDB MAP |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.63 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 42688 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |