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Open data
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Basic information
Entry | ![]() | |||||||||
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Title | Cryo-EM density of BIRC6/casp-7 (clusters) | |||||||||
![]() | main map (consensus refine) | |||||||||
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![]() | Ubiquitin / E3 ligase / Apoptosis / Autophagy / IAP / LIGASE | |||||||||
Function / homology | ![]() caspase-7 / lymphocyte apoptotic process / positive regulation of plasma membrane repair / labyrinthine layer development / (E3-independent) E2 ubiquitin-conjugating enzyme / cellular response to staurosporine / ALK mutants bind TKIs / SMAC, XIAP-regulated apoptotic response / Activation of caspases through apoptosome-mediated cleavage / Flemming body ...caspase-7 / lymphocyte apoptotic process / positive regulation of plasma membrane repair / labyrinthine layer development / (E3-independent) E2 ubiquitin-conjugating enzyme / cellular response to staurosporine / ALK mutants bind TKIs / SMAC, XIAP-regulated apoptotic response / Activation of caspases through apoptosome-mediated cleavage / Flemming body / SMAC (DIABLO) binds to IAPs / SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes / fibroblast apoptotic process / execution phase of apoptosis / Apoptotic cleavage of cellular proteins / microtubule organizing center / ubiquitin conjugating enzyme activity / cysteine-type endopeptidase inhibitor activity / Caspase-mediated cleavage of cytoskeletal proteins / response to UV / striated muscle cell differentiation / cysteine-type peptidase activity / protein maturation / regulation of cytokinesis / negative regulation of extrinsic apoptotic signaling pathway / trans-Golgi network / protein catabolic process / protein processing / fibrillar center / spindle pole / ubiquitin-protein transferase activity / Signaling by ALK fusions and activated point mutants / positive regulation of neuron apoptotic process / peptidase activity / regulation of cell population proliferation / heart development / cellular response to lipopolysaccharide / midbody / neuron apoptotic process / aspartic-type endopeptidase activity / cell population proliferation / endosome / protein ubiquitination / defense response to bacterium / protein phosphorylation / cell division / cysteine-type endopeptidase activity / apoptotic process / positive regulation of cell population proliferation / centrosome / negative regulation of apoptotic process / proteolysis / extracellular space / RNA binding / nucleoplasm / metal ion binding / nucleus / membrane / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.01 Å | |||||||||
![]() | 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 | ![]() | 157.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 47.2 KB 47.2 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 14.3 KB | Display | ![]() |
Images | ![]() | 114 KB | ||
Masks | ![]() ![]() | 166.4 MB 52.7 MB | ![]() | |
Filedesc metadata | ![]() | 9.6 KB | ||
Others | ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() | 157.2 MB 157.3 MB 157.3 MB 157.3 MB 157.3 MB 157.3 MB 157.3 MB 157.3 MB 157.3 MB 157.3 MB 154.3 MB 154.3 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8e2dC ![]() 8e2eC ![]() 8e2fC ![]() 8e2gC ![]() 8e2hC ![]() 8e2iC ![]() 8e2jC ![]() 8e2kC 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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Annotation | main map (consensus refine) | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
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
+Mask #2
+Additional map: cluster 1
+Additional map: cluster 10
+Additional map: cluster 2
+Additional map: cluster 3
+Additional map: cluster 4
+Additional map: cluster 5
+Additional map: cluster 6
+Additional map: cluster 7
+Additional map: cluster 8
+Additional map: cluster 9
+Half map: half map 1
+Half map: half map 2
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Sample components
-Entire : BIRC6/casp-7
Entire | Name: BIRC6/casp-7 |
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Components |
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-Supramolecule #1: BIRC6/casp-7
Supramolecule | Name: BIRC6/casp-7 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 1.132 MDa |
-Macromolecule #1: Baculoviral IAP repeat-containing protein 6
Macromolecule | Name: Baculoviral IAP repeat-containing protein 6 / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO / EC number: Ligases |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
Sequence | String: MGDWSHPQFE KSGGGSGGLE VLFQGPSRTM VTGGGAAPPG TVTEPLPSVI VLSAGRKMAA AAAAASGPGC SSAAGAGAAG VSEWLVLRDG CMHCDADGLH SLSYHPALNA ILAVTSRGTI KVIDGTSGAT LQASALSAKP GGQVKCQYIS AVDKVIFVDD YAVGCRKDLN ...String: MGDWSHPQFE KSGGGSGGLE VLFQGPSRTM VTGGGAAPPG TVTEPLPSVI VLSAGRKMAA AAAAASGPGC SSAAGAGAAG VSEWLVLRDG CMHCDADGLH SLSYHPALNA ILAVTSRGTI KVIDGTSGAT LQASALSAKP GGQVKCQYIS AVDKVIFVDD YAVGCRKDLN GILLLDTALQ TPVSKQDDVV QLELPVTEAQ QLLSACLEKV DISSTEGYDL FITQLKDGLK NTSHETAANH KVAKWATVTF HLPHHVLKSI ASAIVNELKK INQNVAALPV ASSVMDRLSY LLPSARPELG VGPGRSVDRS LMYSEANRRE TFTSWPHVGY RWAQPDPMAQ AGFYHQPASS GDDRAMCFTC SVCLVCWEPT DEPWSEHERH SPNCPFVKGE HTQNVPLSVT LATSPAQFPC TDGTDRISCF GSGSCPHFLA AATKRGKICI WDVSKLMKVH LKFEINAYDP AIVQQLILSG DPSSGVDSRR PTLAWLEDSS SCSDIPKLEG DSDDLLEDSD SEEHSRSDSV TGHTSQKEAM EVSLDITALS ILQQPEKLQW EIVANVLEDT VKDLEELGAN PCLTNSKSEK TKEKHQEQHN IPFPCLLAGG LLTYKSPATS PISSNSHRSL DGLSRTQGES ISEQGSTDNE SCTNSELNSP LVRRTLPVLL LYSIKESDEK AGKIFSQMNN IMSKSLHDDG FTVPQIIEME LDSQEQLLLQ DPPVTYIQQF ADAAANLTSP DSEKWNSVFP KPGTLVQCLR LPKFAEEENL CIDSITPCAD GIHLLVGLRT CPVESLSAIN QVEALNNLNK LNSALCNRRK GELESNLAVV NGANISVIQH ESPADVQTPL IIQPEQRNVS GGYLVLYKMN YATRIVTLEE EPIKIQHIKD PQDTITSLIL LPPDILDNRE DDCEEPIEDM QLTSKNGFER EKTSDISTLG HLVITTQGGY VKILDLSNFE ILAKVEPPKK EGTEEQDTFV SVIYCSGTDR LCACTKGGEL HFLQIGGTCD DIDEADILVD GSLSKGIEPS SEGSKPLSNP SSPGISGVDL LVDQPFTLEI LTSLVELTRF ETLTPRFSAT VPPCWVEVQQ EQQQRRHPQH LHQQHHGDAA QHTRTWKLQT DSNSWDEHVF ELVLPKACMV GHVDFKFVLN SNITNIPQIQ VTLLKNKAPG LGKVNALNIE VEQNGKPSLV DLNEEMQHMD VEESQCLRLC PFLEDHKEDI LCGPVWLASG LDLSGHAGML TLTSPKLVKG MAGGKYRSFL IHVKAVNERG TEEICNGGMR PVVRLPSLKH QSNKGYSLAS LLAKVAAGKE KSSNVKNENT SGTRKSENLR GCDLLQEVSV TIRRFKKTSI SKERVQRCAM LQFSEFHEKL VNTLCRKTDD GQITEHAQSL VLDTLCWLAG VHSNGPGSSK EGNENLLSKT RKFLSDIVRV CFFEAGRSIA HKCARFLALC ISNGKCDPCQ PAFGPVLLKA LLDNMSFLPA ATTGGSVYWY FVLLNYVKDE DLAGCSTACA SLLTAVSRQL QDRLTPMEAL LQTRYGLYSS PFDPVLFDLE MSGSSCKNVY NSSIGVQSDE IDLSDVLSGN GKVSSCTAAE GSFTSLTGLL EVEPLHFTCV STSDGTRIER DDAMSSFGVT PAVGGLSSGT VGEASTALSS AAQVALQSLS HAMASAEQQL QVLQEKQQQL LKLQQQKAKL EAKLHQTTAA AAAAASAVGP VHNSVPSNPV AAPGFFIHPS DVIPPTPKTT PLFMTPPLTP PNEAVSVVIN AELAQLFPGS VIDPPAVNLA AHNKNSNKSR MNPLGSGLAL AISHASHFLQ PPPHQSIIIE RMHSGARRFV TLDFGRPILL TDVLIPTCGD LASLSIDIWT LGEEVDGRRL VVATDISTHS LILHDLIPPP VCRFMKITVI GRYGSTNARA KIPLGFYYGH TYILPWESEL KLMHDPLKGE GESANQPEID QHLAMMVALQ EDIQCRYNLA CHRLETLLQS IDLPPLNSAN NAQYFLRKPD KAVEEDSRVF SAYQDCIQLQ LQLNLAHNAV QRLKVALGAS RKMLSETSNP EDLIQTSSTE QLRTIIRYLL DTLLSLLHAS NGHSVPAVLQ STFHAQACEE LFKHLCISGT PKIRLHTGLL LVQLCGGERW WGQFLSNVLQ ELYNSEQLLI FPQDRVFMLL SCIGQRSLSN SGVLESLLNL LDNLLSPLQP QLPMHRRTEG VLDIPMISWV VMLVSRLLDY VATVEDEAAA AKKPLNGNQW SFINNNLHTQ SLNRSSKGSS SLDRLYSRKI RKQLVHHKQQ LNLLKAKQKA LVEQMEKEKI QSNKGSSYKL LVEQAKLKQA TSKHFKDLIR LRRTAEWSRS NLDTEVTTAK ESPEIEPLPF TLAHERCISV VQKLVLFLLS MDFTCHADLL LFVCKVLARI ANATRPTIHL CEIVNEPQLE RLLLLLVGTD FNRGDISWGG AWAQYSLTCM LQDILAGELL APVAAEAMEE GTVGDDVGAT AGDSDDSLQQ SSVQLLETID EPLTHDITGA PPLSSLEKDK EIDLELLQDL MEVDIDPLDI DLEKDPLAAK VFKPISSTWY DYWGADYGTY NYNPYIGGLG IPVAKPPANT EKNGSQTVSV SVSQALDARL EVGLEQQAEL MLKMMSTLEA DSILQALTNT SPTLSQSPTG TDDSLLGGLQ AANQTSQLII QLSSVPMLNV CFNKLFSMLQ VHHVQLESLL QLWLTLSLNS SSTGNKENGA DIFLYNANRI PVISLNQASI TSFLTVLAWY PNTLLRTWCL VLHSLTLMTN MQLNSGSSSA IGTQESTAHL LVSDPNLIHV LVKFLSGTSP HGTNQHSPQV GPTATQAMQE FLTRLQVHLS STCPQIFSEF LLKLIHILST ERGAFQTGQG PLDAQVKLLE FTLEQNFEVV SVSTISAVIE SVTFLVHHYI TCSDKVMSRS GSDSSVGARA CFGGLFANLI RPGDAKAVCG EMTRDQLMFD LLKLVNILVQ LPLSGNREYS ARVSVTTNTT DSVSDEEKVS GGKDGNGSST SVQGSPAYVA DLVLANQQIM SQILSALGLC NSSAMAMIIG ASGLHLTKHE NFHGGLDAIS VGDGLFTILT TLSKKASTVH MMLQPILTYM ACGYMGRQGS LATCQLSEPL LWFILRVLDT SDALKAFHDM GGVQLICNNM VTSTRAIVNT ARSMVSTIMK FLDSGPNKAV DSTLKTRILA SEPDNAEGIH NFAPLGTITS SSPTAQPAEV LLQATPPHRR ARSAAWSYIF LPEEAWCDLT IHLPAAVLLK EIHIQPHLAS LATCPSSVSV EVSADGVNML PLSTPVVTSG LTYIKIQLVK AEVASAVCLR LHRPRDASTL GLSQIKLLGL TAFGTTSSAT VNNPFLPSED QVSKTSIGWL RLLHHCLTHI SDLEGMMASA AAPTANLLQT CAALLMSPYC GMHSPNIEVV LVKIGLQSTR IGLKLIDILL RNCAASGSDP TDLNSPLLFG RLNGLSSDST IDILYQLGTT QDPGTKDRIQ ALLKWVSDSA RVAAMKRSGR MNYMCPNSST VEYGLLMPSP SHLHCVAAIL WHSYELLVEY DLPALLDQEL FELLFNWSMS LPCNMVLKKA VDSLLCSMCH VHPNYFSLLM GWMGITPPPV QCHHRLSMTD DSKKQDLSSS LTDDSKNAQA PLALTESHLA TLASSSQSPE AIKQLLDSGL PSLLVRSLAS FCFSHISSSE SIAQSIDISQ DKLRRHHVPQ QCNKMPITAD LVAPILRFLT EVGNSHIMKD WLGGSEVNPL WTALLFLLCH SGSTSGSHNL GAQQTSARSA SLSSAATTGL TTQQRTAIEN ATVAFFLQCI SCHPNNQKLM AQVLCELFQT SPQRGNLPTS GNISGFIRRL FLQLMLEDEK VTMFLQSPCP LYKGRINATS HVIQHPMYGA GHKFRTLHLP VSTTLSDVLD RVSDTPSITA KLISEQKDDK EKKNHEEKEK VKAENGFQDN YSVVVASGLK SQSKRAVSAT PPRPPSRRGR TIPDKIGSTS GAEAANKIIT VPVFHLFHKL LAGQPLPAEM TLAQLLTLLY DRKLPQGYRS IDLTVKLGSR VITDPSLSKT DSYKRLHPEK DHGDLLASCP EDEALTPGDE CMDGILDESL LETCPIQSPL QVFAGMGGLA LIAERLPMLY PEVIQQVSAP VVTSTTQEKP KDSDQFEWVT IEQSGELVYE APETVAAEPP PIKSAVQTMS PIPAHSLAAF GLFLRLPGYA EVLLKERKHA QCLLRLVLGV TDDGEGSHIL QSPSANVLPT LPFHVLRSLF STTPLTTDDG VLLRRMALEI GALHLILVCL SALSHHSPRV PNSSVNQTEP QVSSSHNPTS TEEQQLYWAK GTGFGTGSTA SGWDVEQALT KQRLEEEHVT CLLQVLASYI NPVSSAVNGE AQSSHETRGQ NSNALPSVLL ELLSQSCLIP AMSSYLRNDS VLDMARHVPL YRALLELLRA IASCAAMVPL LLPLSTENGE EEEEQSECQT SVGTLLAKMK TCVDTYTNRL RSKRENVKTG VKPDASDQEP EGLTLLVPDI QKTAEIVYAA TTSLRQANQE KKLGEYSKKA AMKPKPLSVL KSLEEKYVAV MKKLQFDTFE MVSEDEDGKL GFKVNYHYMS QVKNANDANS AARARRLAQE AVTLSTSLPL SSSSSVFVRC DEERLDIMKV LITGPADTPY ANGCFEFDVY FPQDYPSSPP LVNLETTGGH SVRFNPNLYN DGKVCLSILN TWHGRPEEKW NPQTSSFLQV LVSVQSLILV AEPYFNEPGY ERSRGTPSGT QSSREYDGNI RQATVKWAML EQIRNPSPCF KEVIHKHFYL KRVEIMAQCE EWIADIQQYS SDKRVGRTMS HHAAALKRHT AQLREELLKL PCPEGLDPDT DDAPEVCRAT TGAEETLMHD QVKPSSSKEL PSDFQL UniProtKB: Dual E2 ubiquitin-conjugating enzyme/E3 ubiquitin-protein ligase BIRC6 |
-Macromolecule #2: caspase-7
Macromolecule | Name: caspase-7 / type: protein_or_peptide / ID: 2 / Enantiomer: LEVO / EC number: caspase-7 |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MADDQGCIEE QGVEDSANED SVDAKPDRSS FVPSLFSKKK KNVTMRSIKT TRDRVPTYQY NMNFEKLGKC IIINNKNFDK VTGMGVRNGT DKDAEALFKC FRSLGFDVIV YNDCSCAKMQ DLLKKASEED HTNAACFACI LLSHGEENVI YGKDGVTPIK DLTAHFRGDR ...String: MADDQGCIEE QGVEDSANED SVDAKPDRSS FVPSLFSKKK KNVTMRSIKT TRDRVPTYQY NMNFEKLGKC IIINNKNFDK VTGMGVRNGT DKDAEALFKC FRSLGFDVIV YNDCSCAKMQ DLLKKASEED HTNAACFACI LLSHGEENVI YGKDGVTPIK DLTAHFRGDR CKTLLEKPKL FFIQACRGTE LDDGIQADSG PINDTDANPR YKIPVEADFL FAYSTVPGYY SWRSPGRGSW FVQALCSILE EHGKDLEIMQ ILTRVNDRVA RHFESQSDDP HFHEKKQIPC VVSMLTKELY FSQLEHHHHH H UniProtKB: Caspase-7 |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 3.1 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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Specialist optics | Energy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV |
Details | Data collection in counting mode, using multi-shot scheme (9 holes per stage position, 2 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: 1-51 / Number grids imaged: 1 / Number real images: 18216 / Average exposure time: 2.5 sec. / Average electron dose: 54.387 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 1.9000000000000001 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 105000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
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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