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Open data
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Basic information
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Title | Cryo-EM structure of human BIRC6 in complex with SMAC. | |||||||||
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Function / homology | ![]() activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c / spongiotrophoblast layer development / Release of apoptotic factors from the mitochondria / CD40 receptor complex / labyrinthine layer development / ALK mutants bind TKIs / SMAC, XIAP-regulated apoptotic response / Flemming body / Regulation of the apoptosome activity / SMAC (DIABLO) binds to IAPs ...activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c / spongiotrophoblast layer development / Release of apoptotic factors from the mitochondria / CD40 receptor complex / labyrinthine layer development / ALK mutants bind TKIs / SMAC, XIAP-regulated apoptotic response / Flemming body / Regulation of the apoptosome activity / SMAC (DIABLO) binds to IAPs / SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes / microtubule organizing center / intrinsic apoptotic signaling pathway in response to oxidative stress / cysteine-type endopeptidase inhibitor activity / ubiquitin conjugating enzyme activity / extrinsic apoptotic signaling pathway via death domain receptors / intrinsic apoptotic signaling pathway / regulation of cytokinesis / negative regulation of extrinsic apoptotic signaling pathway / trans-Golgi network / RING-type E3 ubiquitin transferase / mitochondrial intermembrane space / cytoplasmic side of plasma membrane / spindle pole / ubiquitin-protein transferase activity / activation of cysteine-type endopeptidase activity involved in apoptotic process / Signaling by ALK fusions and activated point mutants / regulation of cell population proliferation / midbody / neuron apoptotic process / cell population proliferation / endosome / protein ubiquitination / positive regulation of apoptotic process / cell division / protein phosphorylation / centrosome / positive regulation of cell population proliferation / negative regulation of apoptotic process / apoptotic process / mitochondrion / membrane / nucleus / cytosol Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 7.2 Å | |||||||||
![]() | Ehrmann JF / Grabarczyk DB / Clausen T | |||||||||
Funding support | European Union, 1 items
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![]() | ![]() Title: Structural basis for regulation of apoptosis and autophagy by the BIRC6/SMAC complex. Authors: Julian F Ehrmann / Daniel B Grabarczyk / Maria Heinke / Luiza Deszcz / Robert Kurzbauer / Otto Hudecz / Alexandra Shulkina / Rebeca Gogova / Anton Meinhart / Gijs A Versteeg / Tim Clausen / ![]() Abstract: Inhibitor of apoptosis proteins (IAPs) bind to pro-apoptotic proteases, keeping them inactive and preventing cell death. The atypical ubiquitin ligase BIRC6 is the only essential IAP, additionally ...Inhibitor of apoptosis proteins (IAPs) bind to pro-apoptotic proteases, keeping them inactive and preventing cell death. The atypical ubiquitin ligase BIRC6 is the only essential IAP, additionally functioning as a suppressor of autophagy. We performed a structure-function analysis of BIRC6 in complex with caspase-9, HTRA2, SMAC, and LC3B, which are critical apoptosis and autophagy proteins. Cryo-electron microscopy structures showed that BIRC6 forms a megadalton crescent shape that arcs around a spacious cavity containing receptor sites for client proteins. Multivalent binding of SMAC obstructs client binding, impeding ubiquitination of both autophagy and apoptotic substrates. On the basis of these data, we discuss how the BIRC6/SMAC complex can act as a stress-induced hub to regulate apoptosis and autophagy drivers. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 94.3 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 22.8 KB 22.8 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 10.7 KB | Display | ![]() |
Images | ![]() | 70.1 KB | ||
Masks | ![]() | 103 MB | ![]() | |
Others | ![]() ![]() ![]() | 93.2 MB 81.3 MB 81.3 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8auwMC ![]() 8atuC ![]() 8atxC ![]() 8aukC M: atomic model generated by this map 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
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Voxel size | X=Y=Z: 1.42333 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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-Additional map: B factor blurred 100 A2
File | emd_15675_additional_1.map | ||||||||||||
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Annotation | B factor blurred 100 A2 | ||||||||||||
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-Half map: #2
File | emd_15675_half_map_1.map | ||||||||||||
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-Half map: #1
File | emd_15675_half_map_2.map | ||||||||||||
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Density Histograms |
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Sample components
-Entire : Human BIRC6 homodimer in complex with SMAC homodimer
Entire | Name: Human BIRC6 homodimer in complex with SMAC homodimer |
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Components |
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-Supramolecule #1: Human BIRC6 homodimer in complex with SMAC homodimer
Supramolecule | Name: Human BIRC6 homodimer in complex with SMAC homodimer / type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 1.1 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: RING-type E3 ubiquitin transferase |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 532.009 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MVTGGGAAPP GTVTEPLPSV IVLSAGRKMA AAAAAASGPG CSSAAGAGAA GVSEWLVLRD GCMHCDADGL HSLSYHPALN AILAVTSRG TIKVIDGTSG ATLQASALSA KPGGQVKCQY ISAVDKVIFV DDYAVGCRKD LNGILLLDTA LQTPVSKQDD V VQLELPVT ...String: MVTGGGAAPP GTVTEPLPSV IVLSAGRKMA AAAAAASGPG CSSAAGAGAA GVSEWLVLRD GCMHCDADGL HSLSYHPALN AILAVTSRG TIKVIDGTSG ATLQASALSA KPGGQVKCQY ISAVDKVIFV DDYAVGCRKD LNGILLLDTA LQTPVSKQDD V VQLELPVT EAQQLLSACL EKVDISSTEG YDLFITQLKD GLKNTSHETA ANHKVAKWAT VTFHLPHHVL KSIASAIVNE LK KINQNVA ALPVASSVMD RLSYLLPSAR PELGVGPGRS VDRSLMYSEA NRRETFTSWP HVGYRWAQPD PMAQAGFYHQ PAS SGDDRA MCFTCSVCLV CWEPTDEPWS EHERHSPNCP FVKGEHTQNV PLSVTLATSP AQFPCTDGTD RISCFGSGSC PHFL AAATK RGKICIWDVS KLMKVHLKFE INAYDPAIVQ QLILSGDPSS GVDSRRPTLA WLEDSSSCSD IPKLEGDSDD LLEDS DSEE HSRSDSVTGH TSQKEAMEVS LDITALSILQ QPEKLQWEIV ANVLEDTVKD LEELGANPCL TNSKSEKTKE KHQEQH NIP FPCLLAGGLL TYKSPATSPI SSNSHRSLDG LSRTQGESIS EQGSTDNESC TNSELNSPLV RRTLPVLLLY SIKESDE KA GKIFSQMNNI MSKSLHDDGF TVPQIIEMEL DSQEQLLLQD PPVTYIQQFA DAAANLTSPD SEKWNSVFPK PGTLVQCL R LPKFAEEENL CIDSITPCAD GIHLLVGLRT CPVESLSAIN QVEALNNLNK LNSALCNRRK GELESNLAVV NGANISVIQ HESPADVQTP LIIQPEQRNV SGGYLVLYKM NYATRIVTLE EEPIKIQHIK DPQDTITSLI LLPPDILDNR EDDCEEPIED MQLTSKNGF EREKTSDIST LGHLVITTQG GYVKILDLSN FEILAKVEPP KKEGTEEQDT FVSVIYCSGT DRLCACTKGG E LHFLQIGG TCDDIDEADI LVDGSLSKGI EPSSEGSKPL SNPSSPGISG VDLLVDQPFT LEILTSLVEL TRFETLTPRF SA TVPPCWV EVQQEQQQRR HPQHLHQQHH GDAAQHTRTW KLQTDSNSWD EHVFELVLPK ACMVGHVDFK FVLNSNITNI PQI QVTLLK NKAPGLGKVN ALNIEVEQNG KPSLVDLNEE MQHMDVEESQ CLRLCPFLED HKEDILCGPV WLASGLDLSG HAGM LTLTS PKLVKGMAGG KYRSFLIHVK AVNERGTEEI CNGGMRPVVR LPSLKHQSNK GYSLASLLAK VAAGKEKSSN VKNEN TSGT RKSENLRGCD LLQEVSVTIR RFKKTSISKE RVQRCAMLQF SEFHEKLVNT LCRKTDDGQI TEHAQSLVLD TLCWLA GVH SNGPGSSKEG NENLLSKTRK FLSDIVRVCF FEAGRSIAHK CARFLALCIS NGKCDPCQPA FGPVLLKALL DNMSFLP AA TTGGSVYWYF VLLNYVKDED LAGCSTACAS LLTAVSRQLQ DRLTPMEALL QTRYGLYSSP FDPVLFDLEM SGSSCKNV Y NSSIGVQSDE IDLSDVLSGN GKVSSCTAAE GSFTSLTGLL EVEPLHFTCV STSDGTRIER DDAMSSFGVT PAVGGLSSG TVGEASTALS SAAQVALQSL SHAMASAEQQ LQVLQEKQQQ LLKLQQQKAK LEAKLHQTTA AAAAAASAVG PVHNSVPSNP VAAPGFFIH PSDVIPPTPK TTPLFMTPPL TPPNEAVSVV INAELAQLFP GSVIDPPAVN LAAHNKNSNK SRMNPLGSGL A LAISHASH FLQPPPHQSI IIERMHSGAR RFVTLDFGRP ILLTDVLIPT CGDLASLSID IWTLGEEVDG RRLVVATDIS TH SLILHDL IPPPVCRFMK ITVIGRYGST NARAKIPLGF YYGHTYILPW ESELKLMHDP LKGEGESANQ PEIDQHLAMM VAL QEDIQC RYNLACHRLE TLLQSIDLPP LNSANNAQYF LRKPDKAVEE DSRVFSAYQD CIQLQLQLNL AHNAVQRLKV ALGA SRKML SETSNPEDLI QTSSTEQLRT IIRYLLDTLL SLLHASNGHS VPAVLQSTFH AQACEELFKH LCISGTPKIR LHTGL LLVQ LCGGERWWGQ FLSNVLQELY NSEQLLIFPQ DRVFMLLSCI GQRSLSNSGV LESLLNLLDN LLSPLQPQLP MHRRTE GVL DIPMISWVVM LVSRLLDYVA TVEDEAAAAK KPLNGNQWSF INNNLHTQSL NRSSKGSSSL DRLYSRKIRK QLVHHKQ QL NLLKAKQKAL VEQMEKEKIQ SNKGSSYKLL VEQAKLKQAT SKHFKDLIRL RRTAEWSRSN LDTEVTTAKE SPEIEPLP F TLAHERCISV VQKLVLFLLS MDFTCHADLL LFVCKVLARI ANATRPTIHL CEIVNEPQLE RLLLLLVGTD FNRGDISWG GAWAQYSLTC MLQDILAGEL LAPVAAEAME EGTVGDDVGA TAGDSDDSLQ QSSVQLLETI DEPLTHDITG APPLSSLEKD KEIDLELLQ DLMEVDIDPL DIDLEKDPLA AKVFKPISST WYDYWGADYG TYNYNPYIGG LGIPVAKPPA NTEKNGSQTV S VSVSQALD ARLEVGLEQQ AELMLKMMST LEADSILQAL TNTSPTLSQS PTGTDDSLLG GLQAANQTSQ LIIQLSSVPM LN VCFNKLF SMLQVHHVQL ESLLQLWLTL SLNSSSTGNK ENGADIFLYN ANRIPVISLN QASITSFLTV LAWYPNTLLR TWC LVLHSL TLMTNMQLNS GSSSAIGTQE STAHLLVSDP NLIHVLVKFL SGTSPHGTNQ HSPQVGPTAT QAMQEFLTRL QVHL SSTCP QIFSEFLLKL IHILSTERGA FQTGQGPLDA QVKLLEFTLE QNFEVVSVST ISAVIESVTF LVHHYITCSD KVMSR SGSD SSVGARACFG GLFANLIRPG DAKAVCGEMT RDQLMFDLLK LVNILVQLPL SGNREYSARV SVTTNTTDSV SDEEKV SGG KDGNGSSTSV QGSPAYVADL VLANQQIMSQ ILSALGLCNS SAMAMIIGAS GLHLTKHENF HGGLDAISVG DGLFTIL TT LSKKASTVHM MLQPILTYMA CGYMGRQGSL ATCQLSEPLL WFILRVLDTS DALKAFHDMG GVQLICNNMV TSTRAIVN T ARSMVSTIMK FLDSGPNKAV DSTLKTRILA SEPDNAEGIH NFAPLGTITS SSPTAQPAEV LLQATPPHRR ARSAAWSYI FLPEEAWCDL TIHLPAAVLL KEIHIQPHLA SLATCPSSVS VEVSADGVNM LPLSTPVVTS GLTYIKIQLV KAEVASAVCL RLHRPRDAS TLGLSQIKLL GLTAFGTTSS ATVNNPFLPS EDQVSKTSIG WLRLLHHCLT HISDLEGMMA SAAAPTANLL Q TCAALLMS PYCGMHSPNI EVVLVKIGLQ STRIGLKLID ILLRNCAASG SDPTDLNSPL LFGRLNGLSS DSTIDILYQL GT TQDPGTK DRIQALLKWV SDSARVAAMK RSGRMNYMCP NSSTVEYGLL MPSPSHLHCV AAILWHSYEL LVEYDLPALL DQE LFELLF NWSMSLPCNM VLKKAVDSLL CSMCHVHPNY FSLLMGWMGI TPPPVQCHHR LSMTDDSKKQ DLSSSLTDDS KNAQ APLAL TESHLATLAS SSQSPEAIKQ LLDSGLPSLL VRSLASFCFS HISSSESIAQ SIDISQDKLR RHHVPQQCNK MPITA DLVA PILRFLTEVG NSHIMKDWLG GSEVNPLWTA LLFLLCHSGS TSGSHNLGAQ QTSARSASLS SAATTGLTTQ QRTAIE NAT VAFFLQCISC HPNNQKLMAQ VLCELFQTSP QRGNLPTSGN ISGFIRRLFL QLMLEDEKVT MFLQSPCPLY KGRINAT SH VIQHPMYGAG HKFRTLHLPV STTLSDVLDR VSDTPSITAK LISEQKDDKE KKNHEEKEKV KAENGFQDNY SVVVASGL K SQSKRAVSAT PPRPPSRRGR TIPDKIGSTS GAEAANKIIT VPVFHLFHKL LAGQPLPAEM TLAQLLTLLY DRKLPQGYR SIDLTVKLGS RVITDPSLSK TDSYKRLHPE KDHGDLLASC PEDEALTPGD ECMDGILDES LLETCPIQSP LQVFAGMGGL ALIAERLPM LYPEVIQQVS APVVTSTTQE KPKDSDQFEW VTIEQSGELV YEAPETVAAE PPPIKSAVQT MSPIPAHSLA A FGLFLRLP GYAEVLLKER KHAQCLLRLV LGVTDDGEGS HILQSPSANV LPTLPFHVLR SLFSTTPLTT DDGVLLRRMA LE IGALHLI LVCLSALSHH SPRVPNSSVN QTEPQVSSSH NPTSTEEQQL YWAKGTGFGT GSTASGWDVE QALTKQRLEE EHV TCLLQV LASYINPVSS AVNGEAQSSH ETRGQNSNAL PSVLLELLSQ SCLIPAMSSY LRNDSVLDMA RHVPLYRALL ELLR AIASC AAMVPLLLPL STENGEEEEE QSECQTSVGT LLAKMKTCVD TYTNRLRSKR ENVKTGVKPD ASDQEPEGLT LLVPD IQKT AEIVYAATTS LRQANQEKKL GEYSKKAAMK PKPLSVLKSL EEKYVAVMKK LQFDTFEMVS EDEDGKLGFK VNYHYM SQV KNANDANSAA RARRLAQEAV TLSTSLPLSS SSSVFVRCDE ERLDIMKVLI TGPADTPYAN GCFEFDVYFP QDYPSSP PL VNLETTGGHS VRFNPNLYND GKVCLSILNT WHGRPEEKWN PQTSSFLQVL VSVQSLILVA EPYFNEPGYE RSRGTPSG T QSSREYDGNI RQATVKWAML EQIRNPSPCF KEVIHKHFYL KRVEIMAQCE EWIADIQQYS SDKRVGRTMS HHAAALKRH TAQLREELLK LPCPEGLDPD TDDAPEVCRA TTGAEETLMH DQVKPSSSKE LPSDFQLSAW SHPQFEK |
-Macromolecule #2: Diablo IAP-binding mitochondrial protein
Macromolecule | Name: Diablo IAP-binding mitochondrial protein / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 20.787098 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: AVPIAQKSEP HSLSSEALMR RAVSLVTDST STFLSQTTYA LIEAITEYTK AVYTLTSLYR QYTSLLGKMN SEEEDEVWQV IIGARAEMT SKHQEYLKLE TTWMTAVGLS EMAAEAAYQT GADQASITAR NHIQLVKLQV EEVHQLSRKA ETKLAEAQIE E LRQKTQEE GEERAESEQE AYLRED |
-Macromolecule #3: ZINC ION
Macromolecule | Name: ZINC ION / type: ligand / ID: 3 / Number of copies: 2 / Formula: ZN |
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Molecular weight | Theoretical: 65.409 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.2 mg/mL |
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Buffer | pH: 7.5 |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.5 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |