+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-26813 | |||||||||
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Title | IgA1 Protease with IgA1 substrate | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information secretory dimeric IgA immunoglobulin complex / monomeric IgA immunoglobulin complex / secretory IgA immunoglobulin complex / glomerular filtration / IgA immunoglobulin complex / IgG immunoglobulin complex / positive regulation of respiratory burst / Scavenging of heme from plasma / immunoglobulin complex, circulating / immunoglobulin receptor binding ...secretory dimeric IgA immunoglobulin complex / monomeric IgA immunoglobulin complex / secretory IgA immunoglobulin complex / glomerular filtration / IgA immunoglobulin complex / IgG immunoglobulin complex / positive regulation of respiratory burst / Scavenging of heme from plasma / immunoglobulin complex, circulating / immunoglobulin receptor binding / serine-type peptidase activity / 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 | Gemella haemolysans (bacteria) / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.56 Å | |||||||||
Authors | Eisenmesser ZE / Zheng H | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Commun Biol / Year: 2022 Title: A substrate-induced gating mechanism is conserved among Gram-positive IgA1 metalloproteases. Authors: Jasmina S Redzic / Jeremy Rahkola / Norman Tran / Todd Holyoak / Eunjeong Lee / Antonio Javier Martín-Galiano / Nancy Meyer / Hongjin Zheng / Elan Eisenmesser / Abstract: The mucosal adaptive immune response is dependent on the production of IgA antibodies and particularly IgA1, yet opportunistic bacteria have evolved mechanisms to specifically block this response by ...The mucosal adaptive immune response is dependent on the production of IgA antibodies and particularly IgA1, yet opportunistic bacteria have evolved mechanisms to specifically block this response by producing IgA1 proteases (IgA1Ps). Our lab was the first to describe the structures of a metal-dependent IgA1P (metallo-IgA1P) produced from Gram-positive Streptococcus pneumoniae both in the absence and presence of its IgA1 substrate through cryo-EM single particle reconstructions. This prior study revealed an active-site gating mechanism reliant on substrate-induced conformational changes to the enzyme that begged the question of whether such a mechanism is conserved among the wider Gram-positive metallo-IgA1P subfamily of virulence factors. Here, we used cryo-EM to characterize the metallo-IgA1P of a more distantly related family member from Gemella haemolysans, an emerging opportunistic pathogen implicated in meningitis, endocarditis, and more recently bacteremia in the elderly. While the substrate-free structures of these two metallo-IgA1Ps exhibit differences in the relative starting positions of the domain responsible for gating substrate, the enzymes have similar domain orientations when bound to IgA1. Together with biochemical studies that indicate these metallo-IgA1Ps have similar binding affinities and activities, these data indicate that metallo-IgA1P binding requires the specific IgA1 substrate to open the enzymes for access to their active site and thus, largely conform to an "induced fit" model. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_26813.map.gz | 165.8 MB | EMDB map data format | |
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Header (meta data) | emd-26813-v30.xml emd-26813.xml | 18.6 KB 18.6 KB | Display Display | EMDB header |
Images | emd_26813.png | 444.2 KB | ||
Masks | emd_26813_msk_1.map | 325 MB | Mask map | |
Others | emd_26813_half_map_1.map.gz emd_26813_half_map_2.map.gz | 301.5 MB 301.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-26813 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-26813 | HTTPS FTP |
-Validation report
Summary document | emd_26813_validation.pdf.gz | 782 KB | Display | EMDB validaton report |
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Full document | emd_26813_full_validation.pdf.gz | 781.5 KB | Display | |
Data in XML | emd_26813_validation.xml.gz | 17.1 KB | Display | |
Data in CIF | emd_26813_validation.cif.gz | 20.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26813 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26813 | HTTPS FTP |
-Related structure data
Related structure data | 7uvlMC 7uvkC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_26813.map.gz / Format: CCP4 / Size: 325 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.802 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_26813_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_26813_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_26813_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : IgA1 Protease with IgA1 substrate
Entire | Name: IgA1 Protease with IgA1 substrate |
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Components |
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-Supramolecule #1: IgA1 Protease with IgA1 substrate
Supramolecule | Name: IgA1 Protease with IgA1 substrate / type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Gemella haemolysans (bacteria) |
-Macromolecule #1: LPXTG-motif cell wall anchor domain protein
Macromolecule | Name: LPXTG-motif cell wall anchor domain protein / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Gemella haemolysans (bacteria) |
Molecular weight | Theoretical: 146.820328 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: DEKKDDIKEE KQVDKKLELR NISNVELYTL ENNKYRHVSS LSSVPTNPEA YFMKVKSENF KDVMLPVKSI ESARKDNQDV YKIVGQAND LIQHENNITL ENYTYYLPKT VNSENGVYTS FKNLVDAMNI NPYGTFRLGA TMDAREVELS DGQESYINKE F SGKLIGEN ...String: DEKKDDIKEE KQVDKKLELR NISNVELYTL ENNKYRHVSS LSSVPTNPEA YFMKVKSENF KDVMLPVKSI ESARKDNQDV YKIVGQAND LIQHENNITL ENYTYYLPKT VNSENGVYTS FKNLVDAMNI NPYGTFRLGA TMDAREVELS DGQESYINKE F SGKLIGEN KGKYYAIYNL KKPLFKALSH ATIQDLSIKE ANVSSKEDAA TIAKEAKNDT TIANVHSSGV IAGERSIGGL IS QVTDSTI SNSSFTGRIT NTYDTTATYQ IGGLVGKLSG VGALIEKSIS SIDMATNANT GDQVVGGVAG VVDKKATIRN SYV EGNLNN VKPFGKVGGV VGNLWDRETS EVSNSGNLTN VLSDVNVTNG NAIAGYDFNG IKATNTYSNK NNKVVKVVQV DDEV LSKDS EEQRGTVLEN NIVLEKKIEL VPKKNTKIED FNFSSRYETD YKNLKDADVS RLRVYKNIEK LLPFYNRETI VKYGN LVDA NNTLYTKDLV SVVPMKDKEV ISDINKNKTS INKLLLHYSD NTSQTLDIKY LQDFSKVAEY EIANTKLIYT PNTLLH SYN NIVKAVLNDL KSVQYDSDAV RKVLDISSNI KLTELYLDEQ FTKTKANIED SLSKLLSADA VIAENSNSII DNYVIEK IK NNKEALLLGL TYLERWYNFK YDNTSAKDLV LYHLDFFGKS NSSALDNVIE LGKSGFNNLL AKNNVITYNV LLSKNYGT E GLFKALEGYR KVFLPNVSNN DWFKTQSKAY IVEEKSTIPE VSSKQSKQGT EHSIGVYDRL TSPSWKYQSM VLPLLTLPE EKMIFMIANI STIGFGAYDR YRSSEYPKGD KLNRFVEENA QAAAKRFRDH YDYWYKILDK ENKEKLFRSV LVYDAFRFGN DTNKETQEA NFETNNPVIK NFFGPAGNNV VHNKHGAYAT GDAFYYMAYR MLDKSGAVTY THAMTHNSDR EIYLGGYGRR S GLGPEFYA KGLLQAPDHS YDPTITINSV LKYDDSENST RLQIADPTQR FTNVEDLHNY MHNMFDLIYT LEILEGRAVA KL DYNEKND LLRKIENIYK KDPDGNSVYA TNAVRRLTSD EIKNLTSFDK LIENDVITRR GYIDQGEYER NGYHTINLFS PIY SALSSK IGTPGDLMGR RMAFELLAAK GYKEGMVPYI SNQYEKEAKD RGSKIRSYGK EIGLVTDDLV LEKVFNKKYG SWVE FKKDM YKERVEQFSK LNRVSFFDPN GPWGRQKNVT VNNISVLEKM IETAVREDAE DFTAQVYPDT NSRVLKLKKA IFKAY LDQT KDFRTSIFGG K |
-Macromolecule #2: Immunoglobulin alpha-1 heavy constant
Macromolecule | Name: Immunoglobulin alpha-1 heavy constant / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 22.784846 KDa |
Recombinant expression | Organism: Mus sp. (mice) |
Sequence | String: CHPRLSLHRP ALEDLLLGSE ANLTCTLTGL RDASGVTFTW TPSSGKSAVQ GPPERDLCGC YSVSSVLPGC AEPWNHGKTF TCTAAYPES KTPLTATLSK SGNTFRPEVH LLPPPSEELA LNELVTLTCL ARGFSPKDVL VRWLQGSQEL PREKYLTWAS R QEPSQGTT ...String: CHPRLSLHRP ALEDLLLGSE ANLTCTLTGL RDASGVTFTW TPSSGKSAVQ GPPERDLCGC YSVSSVLPGC AEPWNHGKTF TCTAAYPES KTPLTATLSK SGNTFRPEVH LLPPPSEELA LNELVTLTCL ARGFSPKDVL VRWLQGSQEL PREKYLTWAS R QEPSQGTT TFAVTSILRV AAEDWKKGDT FSCMVGHEAL PLAFTQKTID R |
-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: Homo sapiens (human) |
Molecular weight | Theoretical: 24.009725 KDa |
Recombinant expression | Organism: Mus sp. (mice) |
Sequence | String: DIVMTQSPLS LSVTPGEPAS ISCRSSQSLL RRDGHNDLEW YLQKPGQSPQ PLIYLGSTRA SGVPDRFSGS GSGTDFTLKI IRVEAEDAG TYYCMQNKQT PLTFGQGTRL EIKRTVAAPS VFIFPPSDEQ LKSGTASVVC LLNNFYPREA KVQWKVDNAL Q SGNSQESV ...String: DIVMTQSPLS LSVTPGEPAS ISCRSSQSLL RRDGHNDLEW YLQKPGQSPQ PLIYLGSTRA SGVPDRFSGS GSGTDFTLKI IRVEAEDAG TYYCMQNKQT PLTFGQGTRL EIKRTVAAPS 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: Homo sapiens (human) |
Molecular weight | Theoretical: 24.554428 KDa |
Recombinant expression | Organism: Mus sp. (mice) |
Sequence | String: EVQLVESGGG LVQPGGSLKL SCAASGFTLS GSNVHWVRQA SGKGLEWVGR IKRNAESDAT AYAASMRGRL TISRDDSKNT AFLQMNSLK SDDTAMYYCV IRGDVYNRQW GQGTLVTVSS ASPTSPKVFP LSLCSTQPDG NVVIACLVQG FFPQEPLSVT W SESGQGVT ...String: EVQLVESGGG LVQPGGSLKL SCAASGFTLS GSNVHWVRQA SGKGLEWVGR IKRNAESDAT AYAASMRGRL TISRDDSKNT AFLQMNSLK SDDTAMYYCV IRGDVYNRQW GQGTLVTVSS ASPTSPKVFP LSLCSTQPDG NVVIACLVQG FFPQEPLSVT W SESGQGVT ARNFPPSQDA SGDLYTTSSQ LTLPATQCLA GKSVTCHVKH YTNPSQDVTV PCPVPSTPPT PSPS |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 Component:
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 49.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: OTHER |
Electron optics | Illumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 5.0 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.56 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 205808 |
Initial angle assignment | Type: OTHER |
Final angle assignment | Type: OTHER |