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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-22204 | |||||||||
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Title | Streptococcus Pneumoniae IgA1 Protease with IgA1 substrate | |||||||||
![]() | IgA1 Protease with IgA1 substrate | |||||||||
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Function / homology | ![]() IgA-specific metalloendopeptidase / secretory dimeric IgA immunoglobulin complex / monomeric IgA immunoglobulin complex / secretory IgA immunoglobulin complex / transcription factor TFIIIB complex / RNA polymerase III preinitiation complex assembly / glomerular filtration / TFIIIC-class transcription factor complex binding / IgA immunoglobulin complex / IgG immunoglobulin complex ...IgA-specific metalloendopeptidase / secretory dimeric IgA immunoglobulin complex / monomeric IgA immunoglobulin complex / secretory IgA immunoglobulin complex / transcription factor TFIIIB complex / RNA polymerase III preinitiation complex assembly / glomerular filtration / TFIIIC-class transcription factor complex binding / IgA immunoglobulin complex / IgG immunoglobulin complex / positive regulation of respiratory burst / Scavenging of heme from plasma / immunoglobulin complex, circulating / immunoglobulin receptor binding / complement activation, classical pathway / Cell surface interactions at the vascular wall / antigen binding / B cell receptor signaling pathway / metalloendopeptidase activity / antibacterial humoral response / adaptive immune response / blood microparticle / immune response / proteolysis / extracellular space / zinc ion binding / extracellular exosome / extracellular region / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.0 Å | |||||||||
![]() | Eisenmesser EZ / Zheng H | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Mechanism and inhibition of Streptococcus pneumoniae IgA1 protease. Authors: Zhiming Wang / Jeremy Rahkola / Jasmina S Redzic / Ying-Chih Chi / Norman Tran / Todd Holyoak / Hongjin Zheng / Edward Janoff / Elan Eisenmesser / ![]() ![]() Abstract: Opportunistic pathogens such as Streptococcus pneumoniae secrete a giant metalloprotease virulence factor responsible for cleaving host IgA1, yet the molecular mechanism has remained unknown since ...Opportunistic pathogens such as Streptococcus pneumoniae secrete a giant metalloprotease virulence factor responsible for cleaving host IgA1, yet the molecular mechanism has remained unknown since their discovery nearly 30 years ago despite the potential for developing vaccines that target these enzymes to block infection. Here we show through a series of cryo-electron microscopy single particle reconstructions how the Streptococcus pneumoniae IgA1 protease facilitates IgA1 substrate recognition and how this can be inhibited. Specifically, the Streptococcus pneumoniae IgA1 protease subscribes to an active-site-gated mechanism where a domain undergoes a 10.0 Å movement to facilitate cleavage. Monoclonal antibody binding inhibits this conformational change, providing a direct means to block infection at the host interface. These structural studies explain decades of biological and biochemical studies and provides a general strategy to block Streptococcus pneumoniae IgA1 protease activity to potentially prevent infection. | |||||||||
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 | ![]() | 40.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 14.9 KB 14.9 KB | Display Display | ![]() |
Images | ![]() | 86 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 469.6 KB | Display | ![]() |
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Full document | ![]() | 469.2 KB | Display | |
Data in XML | ![]() | 6 KB | Display | |
Data in CIF | ![]() | 6.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6xjaMC ![]() 6xjbC ![]() 7jgjC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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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 | IgA1 Protease with IgA1 substrate | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.59 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : IgA1 Protease and IgA1 substrate
Entire | Name: IgA1 Protease and IgA1 substrate |
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Components |
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-Supramolecule #1: IgA1 Protease and IgA1 substrate
Supramolecule | Name: IgA1 Protease and IgA1 substrate / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Molecular weight | Theoretical: 300 KDa |
-Supramolecule #2: Immunoglobulin A1 protease
Supramolecule | Name: Immunoglobulin A1 protease / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() Strain: ATCC BAA-255 / R6 |
Recombinant expression | Organism: ![]() ![]() |
-Supramolecule #3: Immunoglobulin heavy constant alpha 1, Immunoglobulin alpha-1 lig...
Supramolecule | Name: Immunoglobulin heavy constant alpha 1, Immunoglobulin alpha-1 light chain, Immunoglobulin alpha-1 heavy chain type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#4 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Immunoglobulin A1 protease
Macromolecule | Name: Immunoglobulin A1 protease / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: IgA-specific metalloendopeptidase |
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Source (natural) | Organism: ![]() Strain: ATCC BAA-255 / R6 |
Molecular weight | Theoretical: 145.926625 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: GNTTSENGQT EPEKKLELRN VSDIELYSQT NGTYRQHVSL DGIPENTDTY FVKVKSSAFK DVYIPVASIT EEKRNGQSVY KITAKAEKL QQELENKYVD NFTFYLDKKA KEENTNFTSF SNLVKAINQN PSGTYHLAAS LNANEVELGP DERSYIKDTF T GRLIGEKD ...String: GNTTSENGQT EPEKKLELRN VSDIELYSQT NGTYRQHVSL DGIPENTDTY FVKVKSSAFK DVYIPVASIT EEKRNGQSVY KITAKAEKL QQELENKYVD NFTFYLDKKA KEENTNFTSF SNLVKAINQN PSGTYHLAAS LNANEVELGP DERSYIKDTF T GRLIGEKD GKNYAIYNLK KPLFENLSGA TVEKLSLKNV AISGKNDIGS LANEATNGTK IKQVHVDGVL AGERGVGGLL AK ADQSSIA ESSFKGRIVN TYETTDAYNI GGLVGHLTGK NASIAKSKAT VTISSNTNRS DQTVGGLAGL VDQDAHIQNS YAE GDINNV KHFGKVAGVA GYLWDRTSGE EKHAGELTNV LSDVNVTNGN AITGYHYTGM KVANTFSSKA NRVFNVTLEK DEVV SKESF EERGTMLDAS QIVSKKAEIN PLTLPTVEPL STSGKKDSDF SKIAHYQANR ALVYKNIEKL LPFYNKSTIV KYGNL VKEN SLLYQKELLS AVMMKDDQVI TDIVSNKQTA NKLLLHYNDH SSEKFDLKYQ TDFANLAEYN LGNTGLLYTP NQFLYD RDS IVKEVLPELQ KLDYQSDAIR KTLGISPEVK LTELYLEDQF SKTKQNLGDS LKKLLSADAG LASDNSVTRG YLVDKIK NN KEALLLGLTY LERWYNFNYG QVNVKDLVMY HPDFFGKGNT SPLDTLIELG KSGFNNLLAK NNVDTYGISL ASQHGATD L FSTLEHYRKV FLPNTSNNDW FKSETKAYIV EEKSTIEEVK TKQGLAGTKY SIGVYDRITS ATWKYRNMVL PLLTLPERS VFVISTMSSL GFGAYDRYRS SDHKAGKALN DFVEENARET AKRQRDHYDY WYRILDEQSR EKLYRTILLY DAYKFGDDTT SGKATAEAK FDSSNPAMKN FFGPVGNKVV HNQHGAYATG DGVYYMSYRM LDKDGAITYT HAMTHDSDQD IYLGGYGRRN G LGPEFFAK GLLQAPDQPS DATITINSIL KHSKSDSTEG SRLQVLDPTE RFQNAADLQN YVHNMFDLIY MMEYLEGQSI VN KLSVYQK MAALRKIENK YVKDPADGNE VYATNVVKEL TEAEARNLNS FESLIDHNIL SAREYQSGDY ERNGYYTIKL FAP IYSALS SEKGTPGDLM GRRIAYELLA AKGFKDGMVP YISNQYEEDA KQQGQTINLY GKERGLVTDE LVLKKVFDGK YKTW AEFKT AMYQERVDQF GNLKQVTFKD PTKPWPSYGT KTINNVDELQ ALMDQAVLKD AEGPRWSNYD PEIDSAVHKL KRAIF KAYL DQTNDFRSSI FENKK |
-Macromolecule #2: Immunoglobulin heavy constant alpha 1
Macromolecule | Name: Immunoglobulin heavy constant alpha 1 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 22.887988 KDa |
Sequence | String: CCHPRLSLHR PALEDLLLGS EANLTCTLTG LRDASGVTFT WTPSSGKSAV QGPPERDLCG CYSVSSVLPG CAEPWNHGKT FTCTAAYPE SKTPLTATLS KSGNTFRPEV HLLPPPSEEL ALNELVTLTC LARGFSPKDV LVRWLQGSQE LPREKYLTWA S RQEPSQGT ...String: CCHPRLSLHR PALEDLLLGS EANLTCTLTG LRDASGVTFT WTPSSGKSAV QGPPERDLCG CYSVSSVLPG CAEPWNHGKT FTCTAAYPE SKTPLTATLS KSGNTFRPEV HLLPPPSEEL ALNELVTLTC LARGFSPKDV LVRWLQGSQE LPREKYLTWA S RQEPSQGT TTFAVTSILR VAAEDWKKGD TFSCMVGHEA LPLAFTQKTI DR |
-Macromolecule #3: Immunoglobulin alpha-1 light chain
Macromolecule | Name: Immunoglobulin alpha-1 light chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 21.947256 KDa |
Sequence | String: AAAMAQSPAS LSASAGAAAA IACRSSQAAA AAAAAAALAW YAAKPGAAPA ALIYAASAAA SAVPARFSGS GAGTDFAAAI AAVEAEDAA AYYCAQAAAA AATFGAGTRA EAKRTVAAPS VFIFPPSDEQ LKSGTASVVC LLNNFYPREA KVQWKVDNAL Q SGNSQESV ...String: AAAMAQSPAS LSASAGAAAA IACRSSQAAA AAAAAAALAW YAAKPGAAPA ALIYAASAAA SAVPARFSGS GAGTDFAAAI AAVEAEDAA AYYCAQAAAA AATFGAGTRA EAKRTVAAPS VFIFPPSDEQ LKSGTASVVC LLNNFYPREA KVQWKVDNAL Q SGNSQESV TEQDSKDSTY SLSSTLTLSK ADYEKHKVYA CEVTHQGLSS PVTKSFNRGE C |
-Macromolecule #4: Immunoglobulin alpha-1 heavy chain
Macromolecule | Name: Immunoglobulin alpha-1 heavy chain / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 21.93048 KDa |
Sequence | String: AVALAASGAA AAAPGASLKL SCAASGATAA AAAAAWVRAA AGKALEWVAA IAAAAAAAAA AAAAAAAAAA AISADASAAA AALAAASLA AADTAAYYCA AAGAAAAAAW GQGTLVTVSS ASPTSPKVFP LSLCSTQPDG NVVIACLVQG FFPQEPLSVT W SESGQGVT ...String: AVALAASGAA AAAPGASLKL SCAASGATAA AAAAAWVRAA AGKALEWVAA IAAAAAAAAA AAAAAAAAAA AISADASAAA AALAAASLA AADTAAYYCA AAGAAAAAAW GQGTLVTVSS ASPTSPKVFP LSLCSTQPDG NVVIACLVQG FFPQEPLSVT W SESGQGVT ARNFPPSQDA SGDLYTTSSQ LTLPATQCLA GKSVTCHVKH YTNPSQDVTV PCPAVPTPPT PSPS |
-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: 7 / Details: 20 mM Hepes, pH 7 150 mM NaCl |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 30.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 4.0 Å / Resolution method: FSC 3 SIGMA CUT-OFF / Number images used: 100000 |
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Initial angle assignment | Type: OTHER |
Final angle assignment | Type: OTHER |