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Open data
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Basic information
Entry | ![]() | |||||||||
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Title | Cryo-EM structure of BIRC6/HtrA2-S306A | |||||||||
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Function / homology | ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | Hunkeler M / Fischer ES | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structures of BIRC6-client complexes provide a mechanism of SMAC-mediated release of caspases. Authors: Moritz Hunkeler / Cyrus Y Jin / Eric S Fischer / ![]() Abstract: Tight regulation of apoptosis is essential for metazoan development and prevents diseases such as cancer and neurodegeneration. Caspase activation is central to apoptosis, and inhibitor of apoptosis ...Tight regulation of apoptosis is essential for metazoan development and prevents diseases such as cancer and neurodegeneration. Caspase activation is central to apoptosis, and inhibitor of apoptosis proteins (IAPs) are the principal actors that restrain caspase activity and are therefore attractive therapeutic targets. IAPs, in turn, are regulated by mitochondria-derived proapoptotic factors such as SMAC and HTRA2. Through a series of cryo-electron microscopy structures of full-length human baculoviral IAP repeat-containing protein 6 (BIRC6) bound to SMAC, caspases, and HTRA2, we provide a molecular understanding for BIRC6-mediated caspase inhibition and its release by SMAC. The architecture of BIRC6, together with near-irreversible binding of SMAC, elucidates how the IAP inhibitor SMAC can effectively control a processive ubiquitin ligase to respond to apoptotic stimuli. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 157.2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 27.5 KB 27.5 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 11.6 KB | Display | ![]() |
Images | ![]() | 74.2 KB | ||
Masks | ![]() ![]() | 166.4 MB 52.7 MB | ![]() | |
Filedesc metadata | ![]() | 9.8 KB | ||
Others | ![]() ![]() | 154.6 MB 154.6 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8e2kMC ![]() 8e2dC ![]() 8e2eC ![]() 8e2fC ![]() 8e2gC ![]() 8e2hC ![]() 8e2iC ![]() 8e2jC C: citing same article ( M: atomic model generated by this map |
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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
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Annotation | main map | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.2 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
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-Mask #2
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-Half map: half map 1
File | emd_27841_half_map_1.map | ||||||||||||
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Annotation | half map 1 | ||||||||||||
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-Half map: half map 2
File | emd_27841_half_map_2.map | ||||||||||||
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Annotation | half map 2 | ||||||||||||
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Sample components
-Entire : Baculoviral IAP repeat-containing protein 6
Entire | Name: Baculoviral IAP repeat-containing protein 6 |
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Components |
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-Supramolecule #1: Baculoviral IAP repeat-containing protein 6
Supramolecule | Name: Baculoviral IAP repeat-containing protein 6 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 1.174 MDa |
-Macromolecule #1: Baculoviral IAP repeat-containing protein 6
Macromolecule | Name: Baculoviral IAP repeat-containing protein 6 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO / EC number: ![]() |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 535.317188 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MGDYKDHDGD YKDHDIDYKD DDDKGGGSGG LEVLFQGPSR TMVTGGGAAP PGTVTEPLPS VIVLSAGRKM AAAAAAASGP GCSSAAGAG AAGVSEWLVL RDGCMHCDAD GLHSLSYHPA LNAILAVTSR GTIKVIDGTS GATLQASALS AKPGGQVKCQ Y ISAVDKVI ...String: MGDYKDHDGD YKDHDIDYKD DDDKGGGSGG LEVLFQGPSR TMVTGGGAAP PGTVTEPLPS VIVLSAGRKM AAAAAAASGP GCSSAAGAG AAGVSEWLVL RDGCMHCDAD GLHSLSYHPA LNAILAVTSR GTIKVIDGTS GATLQASALS AKPGGQVKCQ Y ISAVDKVI FVDDYAVGCR KDLNGILLLD TALQTPVSKQ DDVVQLELPV TEAQQLLSAC LEKVDISSTE GYDLFITQLK DG LKNTSHE TAANHKVAKW ATVTFHLPHH VLKSIASAIV NELKKINQNV AALPVASSVM DRLSYLLPSA RPELGVGPGR SVD RSLMYS EANRRETFTS WPHVGYRWAQ PDPMAQAGFY HQPASSGDDR AMCFTCSVCL VCWEPTDEPW SEHERHSPNC PFVK GEHTQ NVPLSVTLAT SPAQFPCTDG TDRISCFGSG SCPHFLAAAT KRGKICIWDV SKLMKVHLKF EINAYDPAIV QQLIL SGDP SSGVDSRRPT LAWLEDSSSC SDIPKLEGDS DDLLEDSDSE EHSRSDSVTG HTSQKEAMEV SLDITALSIL QQPEKL QWE IVANVLEDTV KDLEELGANP CLTNSKSEKT KEKHQEQHNI PFPCLLAGGL LTYKSPATSP ISSNSHRSLD GLSRTQG ES ISEQGSTDNE SCTNSELNSP LVRRTLPVLL LYSIKESDEK AGKIFSQMNN IMSKSLHDDG FTVPQIIEME LDSQEQLL L QDPPVTYIQQ FADAAANLTS PDSEKWNSVF PKPGTLVQCL RLPKFAEEEN LCIDSITPCA DGIHLLVGLR TCPVESLSA INQVEALNNL NKLNSALCNR RKGELESNLA VVNGANISVI QHESPADVQT PLIIQPEQRN VSGGYLVLYK MNYATRIVTL EEEPIKIQH IKDPQDTITS LILLPPDILD NREDDCEEPI EDMQLTSKNG FEREKTSDIS TLGHLVITTQ GGYVKILDLS N FEILAKVE PPKKEGTEEQ DTFVSVIYCS GTDRLCACTK GGELHFLQIG GTCDDIDEAD ILVDGSLSKG IEPSSEGSKP LS NPSSPGI SGVDLLVDQP FTLEILTSLV ELTRFETLTP RFSATVPPCW VEVQQEQQQR RHPQHLHQQH HGDAAQHTRT WKL QTDSNS WDEHVFELVL PKACMVGHVD FKFVLNSNIT NIPQIQVTLL KNKAPGLGKV NALNIEVEQN GKPSLVDLNE EMQH MDVEE SQCLRLCPFL EDHKEDILCG PVWLASGLDL SGHAGMLTLT SPKLVKGMAG GKYRSFLIHV KAVNERGTEE ICNGG MRPV VRLPSLKHQS NKGYSLASLL AKVAAGKEKS SNVKNENTSG TRKSENLRGC DLLQEVSVTI RRFKKTSISK ERVQRC AML QFSEFHEKLV NTLCRKTDDG QITEHAQSLV LDTLCWLAGV HSNGPGSSKE GNENLLSKTR KFLSDIVRVC FFEAGRS IA HKCARFLALC ISNGKCDPCQ PAFGPVLLKA LLDNMSFLPA ATTGGSVYWY FVLLNYVKDE DLAGCSTACA SLLTAVSR Q LQDRLTPMEA LLQTRYGLYS SPFDPVLFDL EMSGSSCKNV YNSSIGVQSD EIDLSDVLSG NGKVSSCTAA EGSFTSLTG LLEVEPLHFT CVSTSDGTRI ERDDAMSSFG VTPAVGGLSS GTVGEASTAL SSAAQVALQS LSHAMASAEQ QLQVLQEKQQ QLLKLQQQK AKLEAKLHQT TAAAAAAASA VGPVHNSVPS NPVAAPGFFI HPSDVIPPTP KTTPLFMTPP LTPPNEAVSV V INAELAQL FPGSVIDPPA VNLAAHNKNS NKSRMNPLGS GLALAISHAS HFLQPPPHQS IIIERMHSGA RRFVTLDFGR PI LLTDVLI PTCGDLASLS IDIWTLGEEV DGRRLVVATD ISTHSLILHD LIPPPVCRFM KITVIGRYGS TNARAKIPLG FYY GHTYIL PWESELKLMH DPLKGEGESA NQPEIDQHLA MMVALQEDIQ CRYNLACHRL ETLLQSIDLP PLNSANNAQY FLRK PDKAV EEDSRVFSAY QDCIQLQLQL NLAHNAVQRL KVALGASRKM LSETSNPEDL IQTSSTEQLR TIIRYLLDTL LSLLH ASNG HSVPAVLQST FHAQACEELF KHLCISGTPK IRLHTGLLLV QLCGGERWWG QFLSNVLQEL YNSEQLLIFP QDRVFM LLS CIGQRSLSNS GVLESLLNLL DNLLSPLQPQ LPMHRRTEGV LDIPMISWVV MLVSRLLDYV ATVEDEAAAA KKPLNGN QW SFINNNLHTQ SLNRSSKGSS SLDRLYSRKI RKQLVHHKQQ LNLLKAKQKA LVEQMEKEKI QSNKGSSYKL LVEQAKLK Q ATSKHFKDLI RLRRTAEWSR SNLDTEVTTA KESPEIEPLP FTLAHERCIS VVQKLVLFLL SMDFTCHADL LLFVCKVLA RIANATRPTI HLCEIVNEPQ LERLLLLLVG TDFNRGDISW GGAWAQYSLT CMLQDILAGE LLAPVAAEAM EEGTVGDDVG ATAGDSDDS LQQSSVQLLE TIDEPLTHDI TGAPPLSSLE KDKEIDLELL QDLMEVDIDP LDIDLEKDPL AAKVFKPISS T WYDYWGAD YGTYNYNPYI GGLGIPVAKP PANTEKNGSQ TVSVSVSQAL DARLEVGLEQ QAELMLKMMS TLEADSILQA LT NTSPTLS QSPTGTDDSL LGGLQAANQT SQLIIQLSSV PMLNVCFNKL FSMLQVHHVQ LESLLQLWLT LSLNSSSTGN KEN GADIFL YNANRIPVIS LNQASITSFL TVLAWYPNTL LRTWCLVLHS LTLMTNMQLN SGSSSAIGTQ ESTAHLLVSD PNLI HVLVK FLSGTSPHGT NQHSPQVGPT ATQAMQEFLT RLQVHLSSTC PQIFSEFLLK LIHILSTERG AFQTGQGPLD AQVKL LEFT LEQNFEVVSV STISAVIESV TFLVHHYITC SDKVMSRSGS DSSVGARACF GGLFANLIRP GDAKAVCGEM TRDQLM FDL LKLVNILVQL PLSGNREYSA RVSVTTNTTD SVSDEEKVSG GKDGNGSSTS VQGSPAYVAD LVLANQQIMS QILSALG LC NSSAMAMIIG ASGLHLTKHE NFHGGLDAIS VGDGLFTILT TLSKKASTVH MMLQPILTYM ACGYMGRQGS LATCQLSE P LLWFILRVLD TSDALKAFHD MGGVQLICNN MVTSTRAIVN TARSMVSTIM KFLDSGPNKA VDSTLKTRIL ASEPDNAEG IHNFAPLGTI TSSSPTAQPA EVLLQATPPH RRARSAAWSY IFLPEEAWCD LTIHLPAAVL LKEIHIQPHL ASLATCPSSV SVEVSADGV NMLPLSTPVV TSGLTYIKIQ LVKAEVASAV CLRLHRPRDA STLGLSQIKL LGLTAFGTTS SATVNNPFLP S EDQVSKTS IGWLRLLHHC LTHISDLEGM MASAAAPTAN LLQTCAALLM SPYCGMHSPN IEVVLVKIGL QSTRIGLKLI DI LLRNCAA SGSDPTDLNS PLLFGRLNGL SSDSTIDILY QLGTTQDPGT KDRIQALLKW VSDSARVAAM KRSGRMNYMC PNS STVEYG LLMPSPSHLH CVAAILWHSY ELLVEYDLPA LLDQELFELL FNWSMSLPCN MVLKKAVDSL LCSMCHVHPN YFSL LMGWM GITPPPVQCH HRLSMTDDSK KQDLSSSLTD DSKNAQAPLA LTESHLATLA SSSQSPEAIK QLLDSGLPSL LVRSL ASFC FSHISSSESI AQSIDISQDK LRRHHVPQQC NKMPITADLV APILRFLTEV GNSHIMKDWL GGSEVNPLWT ALLFLL CHS GSTSGSHNLG AQQTSARSAS LSSAATTGLT TQQRTAIENA TVAFFLQCIS CHPNNQKLMA QVLCELFQTS PQRGNLP TS GNISGFIRRL FLQLMLEDEK VTMFLQSPCP LYKGRINATS HVIQHPMYGA GHKFRTLHLP VSTTLSDVLD RVSDTPSI T AKLISEQKDD KEKKNHEEKE KVKAENGFQD NYSVVVASGL KSQSKRAVSA TPPRPPSRRG RTIPDKIGST SGAEAANKI ITVPVFHLFH KLLAGQPLPA EMTLAQLLTL LYDRKLPQGY RSIDLTVKLG SRVITDPSLS KTDSYKRLHP EKDHGDLLAS CPEDEALTP GDECMDGILD ESLLETCPIQ SPLQVFAGMG GLALIAERLP MLYPEVIQQV SAPVVTSTTQ EKPKDSDQFE W VTIEQSGE LVYEAPETVA AEPPPIKSAV QTMSPIPAHS LAAFGLFLRL PGYAEVLLKE RKHAQCLLRL VLGVTDDGEG SH ILQSPSA NVLPTLPFHV LRSLFSTTPL TTDDGVLLRR MALEIGALHL ILVCLSALSH HSPRVPNSSV NQTEPQVSSS HNP TSTEEQ QLYWAKGTGF GTGSTASGWD VEQALTKQRL EEEHVTCLLQ VLASYINPVS SAVNGEAQSS HETRGQNSNA LPSV LLELL SQSCLIPAMS SYLRNDSVLD MARHVPLYRA LLELLRAIAS CAAMVPLLLP LSTENGEEEE EQSECQTSVG TLLAK MKTC VDTYTNRLRS KRENVKTGVK PDASDQEPEG LTLLVPDIQK TAEIVYAATT SLRQANQEKK LGEYSKKAAM KPKPLS VLK SLEEKYVAVM KKLQFDTFEM VSEDEDGKLG FKVNYHYMSQ VKNANDANSA ARARRLAQEA VTLSTSLPLS SSSSVFV RC DEERLDIMKV LITGPADTPY ANGCFEFDVY FPQDYPSSPP LVNLETTGGH SVRFNPNLYN DGKVCLSILN TWHGRPEE K WNPQTSSFLQ VLVSVQSLIL VAEPYFNEPG YERSRGTPSG TQSSREYDGN IRQATVKWAM LEQIRNPSPC FKEVIHKHF YLKRVEIMAQ CEEWIADIQQ YSSDKRVGRT MSHHAAALKR HTAQLREELL KLPCPEGLDP DTDDAPEVCR ATTGAEETLM HDQVKPSSS KELPSDFQL UniProtKB: Baculoviral IAP repeat-containing protein 6 |
-Macromolecule #2: Serine protease HTRA2, mitochondrial
Macromolecule | Name: Serine protease HTRA2, mitochondrial / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO / EC number: ![]() |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 35.961887 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: MAVPSPPPAS PRSQYNFIAD VVEKTAPAVV YIEILDRHPF LGREVPISNG SGFVVAADGL IVTNAHVVAD RRRVRVRLLS GDTYEAVVT AVDPVADIAT LRIQTKEPLP TLPLGRSADV RQGEFVVAMG SPFALQNTIT SGIVSSAQRP ARDLGLPQTN V EYIQTDAA ...String: MAVPSPPPAS PRSQYNFIAD VVEKTAPAVV YIEILDRHPF LGREVPISNG SGFVVAADGL IVTNAHVVAD RRRVRVRLLS GDTYEAVVT AVDPVADIAT LRIQTKEPLP TLPLGRSADV RQGEFVVAMG SPFALQNTIT SGIVSSAQRP ARDLGLPQTN V EYIQTDAA IDFGNAGGPL VNLDGEVIGV NTMKVTAGIS FAIPSDRLRE FLHRGEKKNS SSGISGSQRR YIGVMMLTLS PS ILAELQL REPSFPDVQH GVLIHKVILG SPAHRAGLRP GDVILAIGEQ MVQNAEDVYE AVRTQSQLAV QIRRGRETLT LYV TPEVTE HHHHHH UniProtKB: Serine protease HTRA2, mitochondrial |
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Concentration | 1 mg/mL | ||||||||||||
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Buffer | pH: 7.4 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Support film - Film thickness: 12 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 60 sec. / Pretreatment - Atmosphere: AIR / Pretreatment - Pressure: 0.039 kPa | ||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 90 % / Chamber temperature: 283.15 K / Instrument: LEICA EM GP | ||||||||||||
Details | added CHAPSO to 0.4 mM |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Specialist optics | Energy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Details | Data collection in counting mode, using multi-shot scheme (9 holes per stage position, 3 movies per hole) |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Detector mode: COUNTING / Digitization - Dimensions - Width: 5760 pixel / Digitization - Dimensions - Height: 4092 pixel / Digitization - Frames/image: 1-50 / Number grids imaged: 1 / Number real images: 15309 / Average exposure time: 2.5 sec. / Average electron dose: 60.659 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: OTHER |
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Output model | ![]() PDB-8e2k: |