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- EMDB-26813: IgA1 Protease with IgA1 substrate -

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ID or keywords:

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Basic information

Entry
Database: EMDB / ID: EMD-26813
TitleIgA1 Protease with IgA1 substrate
Map data
Sample
  • Complex: IgA1 Protease with IgA1 substrate
    • Protein or peptide: LPXTG-motif cell wall anchor domain protein
    • Protein or peptide: Immunoglobulin alpha-1 heavy constant
    • Protein or peptide: Immunoglobulin alpha-1 light chain
    • Protein or peptide: Immunoglobulin alpha-1 heavy chain
Function / homology
Function and homology information


secretory dimeric IgA immunoglobulin complex / monomeric IgA immunoglobulin complex / secretory IgA immunoglobulin complex / glomerular filtration / IgA immunoglobulin complex / immunoglobulin complex, circulating / IgG immunoglobulin complex / positive regulation of respiratory burst / Scavenging of heme from plasma / complement activation, classical pathway ...secretory dimeric IgA immunoglobulin complex / monomeric IgA immunoglobulin complex / secretory IgA immunoglobulin complex / glomerular filtration / IgA immunoglobulin complex / immunoglobulin complex, circulating / IgG immunoglobulin complex / positive regulation of respiratory burst / Scavenging of heme from plasma / complement activation, classical pathway / antigen binding / serine-type peptidase activity / Cell surface interactions at the vascular wall / B cell receptor signaling pathway / metalloendopeptidase activity / antibacterial humoral response / blood microparticle / adaptive immune response / immune response / proteolysis / extracellular space / extracellular exosome / zinc ion binding / extracellular region / membrane / plasma membrane
Similarity search - Function
Peptidase M26, N-terminal domain / Peptidase M26, C-terminal domain / M26 IgA1-specific Metallo-endopeptidase N-terminal region / M26 IgA1-specific Metallo-endopeptidase C-terminal region / G5 domain / G5 domain / G5 domain profile. / G5 / Immunoglobulin / Immunoglobulin domain ...Peptidase M26, N-terminal domain / Peptidase M26, C-terminal domain / M26 IgA1-specific Metallo-endopeptidase N-terminal region / M26 IgA1-specific Metallo-endopeptidase C-terminal region / G5 domain / G5 domain / G5 domain profile. / G5 / Immunoglobulin / Immunoglobulin domain / Immunoglobulin/major histocompatibility complex, conserved site / Immunoglobulins and major histocompatibility complex proteins signature. / Immunoglobulin C-Type / Immunoglobulin C1-set / Immunoglobulin C1-set domain / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Peptidase S1, PA clan, chymotrypsin-like fold / Peptidase S1, PA clan / Immunoglobulin-like fold
Similarity search - Domain/homology
LPXTG-motif cell wall anchor domain protein / Immunoglobulin heavy constant alpha 1
Similarity search - Component
Biological speciesGemella haemolysans (bacteria) / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.56 Å
AuthorsEisenmesser ZE / Zheng H
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)R21 AI146295 United States
CitationJournal: 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
DepositionMay 2, 2022-
Header (metadata) releaseNov 23, 2022-
Map releaseNov 23, 2022-
UpdateNov 30, 2022-
Current statusNov 30, 2022Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_26813.png

Downloads & links

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Map

FileDownload / File: emd_26813.map.gz / Format: CCP4 / Size: 325 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 0.802 Å
Density
Contour LevelBy AUTHOR: 0.08
Minimum - Maximum-0.12158503 - 0.35443196
Average (Standard dev.)0.00044306548 (±0.008473598)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions440440440
Spacing440440440
CellA=B=C: 352.88 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_26813_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_26813_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_26813_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : IgA1 Protease with IgA1 substrate

EntireName: IgA1 Protease with IgA1 substrate
Components
  • Complex: IgA1 Protease with IgA1 substrate
    • Protein or peptide: LPXTG-motif cell wall anchor domain protein
    • Protein or peptide: Immunoglobulin alpha-1 heavy constant
    • Protein or peptide: Immunoglobulin alpha-1 light chain
    • Protein or peptide: Immunoglobulin alpha-1 heavy chain

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Supramolecule #1: IgA1 Protease with IgA1 substrate

SupramoleculeName: IgA1 Protease with IgA1 substrate / type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Gemella haemolysans (bacteria)

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Macromolecule #1: LPXTG-motif cell wall anchor domain protein

MacromoleculeName: LPXTG-motif cell wall anchor domain protein / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Gemella haemolysans (bacteria)
Molecular weightTheoretical: 146.820328 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: 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

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Macromolecule #2: Immunoglobulin alpha-1 heavy constant

MacromoleculeName: Immunoglobulin alpha-1 heavy constant / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 22.784846 KDa
Recombinant expressionOrganism: Mus sp. (mice)
SequenceString: 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

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Macromolecule #3: Immunoglobulin alpha-1 light chain

MacromoleculeName: Immunoglobulin alpha-1 light chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 24.009725 KDa
Recombinant expressionOrganism: Mus sp. (mice)
SequenceString: 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

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Macromolecule #4: Immunoglobulin alpha-1 heavy chain

MacromoleculeName: Immunoglobulin alpha-1 heavy chain / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 24.554428 KDa
Recombinant expressionOrganism: Mus sp. (mice)
SequenceString: 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

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.4
Component:
ConcentrationFormulaName
300.0 mMNaClSodium chlorideSodium Chloride
20.0 mMHEPES2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: OTHER
Electron opticsIllumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 5.0 µm / Nominal defocus min: 1.2 µm
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 49.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

6xjb

Initial angle assignmentType: OTHER
Final angle assignmentType: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.56 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 205808

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