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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-12520 | |||||||||||||||
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Title | Cytosolic bridge of an intact ESX-5 inner membrane complex | |||||||||||||||
![]() | -50 Bfactor sharpening of the 3D refinement map. | |||||||||||||||
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Function / homology | ![]() peptidoglycan-based cell wall / ATP hydrolysis activity / DNA binding / ATP binding / plasma membrane Similarity search - Function | |||||||||||||||
Biological species | ![]() ![]() | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.27 Å | |||||||||||||||
![]() | Bunduc CM / Fahrenkamp D / Wald J / Ummels R / Bitter W / Houben ENG / Marlovits TC | |||||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: Structure and dynamics of a mycobacterial type VII secretion system. Authors: Catalin M Bunduc / Dirk Fahrenkamp / Jiri Wald / Roy Ummels / Wilbert Bitter / Edith N G Houben / Thomas C Marlovits / ![]() ![]() Abstract: Mycobacterium tuberculosis is the cause of one of the most important infectious diseases in humans, which leads to 1.4 million deaths every year. Specialized protein transport systems-known as ...Mycobacterium tuberculosis is the cause of one of the most important infectious diseases in humans, which leads to 1.4 million deaths every year. Specialized protein transport systems-known as type VII secretion systems (T7SSs)-are central to the virulence of this pathogen, and are also crucial for nutrient and metabolite transport across the mycobacterial cell envelope. Here we present the structure of an intact T7SS inner-membrane complex of M. tuberculosis. We show how the 2.32-MDa ESX-5 assembly, which contains 165 transmembrane helices, is restructured and stabilized as a trimer of dimers by the MycP protease. A trimer of MycP caps a central periplasmic dome-like chamber that is formed by three EccB dimers, with the proteolytic sites of MycP facing towards the cavity. This chamber suggests a central secretion and processing conduit. Complexes without MycP show disruption of the EccB periplasmic assembly and increased flexibility, which highlights the importance of MycP for complex integrity. Beneath the EccB-MycP chamber, dimers of the EccC ATPase assemble into three bundles of four transmembrane helices each, which together seal the potential central secretion channel. Individual cytoplasmic EccC domains adopt two distinctive conformations that probably reflect different secretion states. Our work suggests a previously undescribed mechanism of protein transport and provides a structural scaffold to aid in the development of drugs against this major human pathogen. | |||||||||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 3.2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 22.4 KB 22.4 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 8.9 KB | Display | ![]() |
Images | ![]() | 97.9 KB | ||
Masks | ![]() | 59.6 MB | ![]() | |
Others | ![]() ![]() ![]() ![]() | 45.8 MB 52.7 MB 45.9 MB 45.9 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 374 KB | Display | ![]() |
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Full document | ![]() | 373.1 KB | Display | |
Data in XML | ![]() | 14.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7nptMC ![]() 7np7C ![]() 7nprC ![]() 7npsC ![]() 7npuC ![]() 7npvC C: citing same article ( M: atomic model generated by this map |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Map
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Annotation | -50 Bfactor sharpening of the 3D refinement map. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
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Density Histograms |
-Additional map: 3D refinement map.
File | emd_12520_additional_1.map | ||||||||||||
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Annotation | 3D refinement map. | ||||||||||||
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-Additional map: 3D refinement map postprocessed with DeepEMhancer.
File | emd_12520_additional_2.map | ||||||||||||
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Annotation | 3D refinement map postprocessed with DeepEMhancer. | ||||||||||||
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Density Histograms |
-Half map: Half2 of 3D refinement map.
File | emd_12520_half_map_1.map | ||||||||||||
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Annotation | Half2 of 3D refinement map. | ||||||||||||
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Density Histograms |
-Half map: Half1 of 3D refinement map.
File | emd_12520_half_map_2.map | ||||||||||||
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Annotation | Half1 of 3D refinement map. | ||||||||||||
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Density Histograms |
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Sample components
-Entire : Cytosolic bridge of an intact ESX-5 inner membrane complex
Entire | Name: Cytosolic bridge of an intact ESX-5 inner membrane complex |
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Components |
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-Supramolecule #1: Cytosolic bridge of an intact ESX-5 inner membrane complex
Supramolecule | Name: Cytosolic bridge of an intact ESX-5 inner membrane complex type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
-Macromolecule #1: ESX-5 secretion system protein EccC5
Macromolecule | Name: ESX-5 secretion system protein EccC5 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() Strain: ATCC 25618 / H37Rv |
Molecular weight | Theoretical: 152.90075 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MKRGFARPTP EKPPVIKPEN IVLSTPLSIP PPEGKPWWLI VVGVVVVGLL GGMVAMVFAS GSHVFGGIGS IFPLFMMVGI MMMMFRGMG GGQQQMSRPK LDAMRAQFML MLDMLRETAQ ESADSMDANY RWFHPAPNTL AAAVGSPRMW ERKPDGKDLN F GVVRVGVG ...String: MKRGFARPTP EKPPVIKPEN IVLSTPLSIP PPEGKPWWLI VVGVVVVGLL GGMVAMVFAS GSHVFGGIGS IFPLFMMVGI MMMMFRGMG GGQQQMSRPK LDAMRAQFML MLDMLRETAQ ESADSMDANY RWFHPAPNTL AAAVGSPRMW ERKPDGKDLN F GVVRVGVG MTRPEVTWGE PQNMPTDIEL EPVTGKALQE FGRYQSVVYN LPKMVSLLVE PWYALVGERE QVLGLMRAII CQ LAFSHGP DHVQMIVVSS DLDQWDWVKW LPHFGDSRRH DAAGNARMVY TSVREFAAEQ AELFAGRGSF TPRHASSSAQ TPT PHTVII ADVDDPQWEY VISAEGVDGV TFFDLTGSSM WTDIPERKLQ FDKTGVIEAL PRDRDTWMVI DDKAWFFALT DQVS IAEAE EFAQKLAQWR LAEAYEEIGQ RVAHIGARDI LSYYGIDDPG NIDFDSLWAS RTDTMGRSRL RAPFGNRSDN GELLF LDMK SLDEGGDGPH GVMSGTTGSG KSTLVRTVIE SLMLSHPPEE LQFVLADLKG GSAVKPFAGV PHVSRIITDL EEDQAL MER FLDALWGEIA RRKAICDSAG VDDAKEYNSV RARMRARGQD MAPLPMLVVV IDEFYEWFRI MPTAVDVLDS IGRQGRA YW IHLMMASQTI ESRAEKLMEN MGYRLVLKAR TAGAAQAAGV PNAVNLPAQA GLGYFRKSLE DIIRFQAEFL WRDYFQPG V SIDGEEAPAL VHSIDYIRPQ LFTNSFTPLE VSVGGPDIEP VVAQPNGEVL ESDDIEGGED EDEEGVRTPK VGTVIIDQL RKIKFEPYRL WQPPLTQPVA IDDLVNRFLG RPWHKEYGSA CNLVFPIGII DRPYKHDQPP WTVDTSGPGA NVLILGAGGS GKTTALQTL ICSAALTHTP QQVQFYCLAY SSTALTTVSR IPHVGEVAGP TDPYGVRRTV AELLALVRER KRSFLECGIA S MEMFRRRK FGGEAGPVPD DGFGDVYLVI DNYRALAEEN EVLIEQVNVI INQGPSFGVH VVVTADRESE LRPPVRSGFG SR IELRLAA VEDAKLVRSR FAKDVPVKPG RGMVAVNYVR LDSDPQAGLH TLVARPALGS TPDNVFECDS VVAAVSRLTS AQA PPVRRL PARFGVEQVR ELASRDTRQG VGAGGIAWAI SELDLAPVYL NFAENSHLMV TGRRECGRTT TLATIMSEIG RLYA PGASS APPPAPGRPS AQVWLVDPRR QLLTALGSDY VERFAYNLDG VVAMMGELAA ALAGREPPPG LSAEELLSRS WWSGP EIFL IVDDIQQLPP GFDSPLHKAV PFVNRAADVG LHVIVTRTFG GWSSAGSDPM LRALHQANAP LLVMDADPDE GFIRGK MKG GPLPRGRGLL MAEDTGVFVQ VAATEVRR |
-Macromolecule #2: ESX-5 secretion system protein EccD5
Macromolecule | Name: ESX-5 secretion system protein EccD5 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() Strain: ATCC 25618 / H37Rv |
Molecular weight | Theoretical: 53.480906 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MTAVADAPQA DIEGVASPQA VVVGVMAGEG VQIGVLLDAN APVSVMTDPL LKVVNSRLRE LGEAPLEATG RGRWALCLVD GAPLRATQS LTEQDVYDGD RLWIRFIADT ERRSQVIEHI STAVASDLSK RFARIDPIVA VQVGASMVAT GVVLATGVLG W WRWHHNTW ...String: MTAVADAPQA DIEGVASPQA VVVGVMAGEG VQIGVLLDAN APVSVMTDPL LKVVNSRLRE LGEAPLEATG RGRWALCLVD GAPLRATQS LTEQDVYDGD RLWIRFIADT ERRSQVIEHI STAVASDLSK RFARIDPIVA VQVGASMVAT GVVLATGVLG W WRWHHNTW LTTIYTAVIG VLVLAVAMLL LMRAKTDADR RVADIMLMSA IMPVTVAAAA APPGPVGSPQ AVLGFGVLTV AA ALALRFT GRRLGIYTTI VIIGALTMLA ALARMVAATS AVTLLSSLLL ICVVAYHAAP ALSRRLAGIR LPVFPSATSR WVF EARPDL PTTVVVSGGS APVLEGPSSV RDVLLQAERA RSFLSGLLTG LGVMVVVCMT SLCDPHTGQR WLPLILAGFT SGFL LLRGR SYVDRWQSIT LAGTAVIIAA AVCVRYALEL SSPLAVSIVA AILVLLPAAG MAAAAHVPHT IYSPLFRKFV EWIEY LCLM PIFPLALWLM NVYAAIRYR |
-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: 8 |
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Vitrification | Cryogen name: ETHANE-PROPANE |
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Electron microscopy
Microscope | TFS KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 59.5 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |