[English] 日本語
Yorodumi
- EMDB-22204: Streptococcus Pneumoniae IgA1 Protease with IgA1 substrate -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-22204
TitleStreptococcus Pneumoniae IgA1 Protease with IgA1 substrate
Map dataIgA1 Protease with IgA1 substrate
Sample
  • Complex: IgA1 Protease and IgA1 substrate
    • Complex: Immunoglobulin A1 protease
      • Protein or peptide: Immunoglobulin A1 protease
    • Complex: Immunoglobulin heavy constant alpha 1, Immunoglobulin alpha-1 light chain, Immunoglobulin alpha-1 heavy chain
      • Protein or peptide: Immunoglobulin heavy constant alpha 1
      • Protein or peptide: Immunoglobulin alpha-1 light chain
      • Protein or peptide: Immunoglobulin alpha-1 heavy chain
Function / homology
Function and homology information


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 / immunoglobulin complex, circulating / Scavenging of heme from plasma / immunoglobulin receptor binding / complement activation, classical pathway / antigen binding / Cell surface interactions at the vascular wall / B cell receptor signaling pathway / metalloendopeptidase activity / antibacterial humoral response / adaptive immune response / blood microparticle / immune response / proteolysis / extracellular space / extracellular exosome / zinc ion binding / extracellular region / membrane / plasma membrane
Similarity search - Function
Peptidase M26, N-terminal domain / GLUG / Peptidase M26, C-terminal domain / M26 IgA1-specific Metallo-endopeptidase N-terminal region / M26 IgA1-specific Metallo-endopeptidase C-terminal region / The GLUG motif / G5 domain / G5 domain / G5 domain profile. / G5 ...Peptidase M26, N-terminal domain / GLUG / Peptidase M26, C-terminal domain / M26 IgA1-specific Metallo-endopeptidase N-terminal region / M26 IgA1-specific Metallo-endopeptidase C-terminal region / The GLUG motif / G5 domain / G5 domain / G5 domain profile. / G5 / YSIRK type signal peptide / YSIRK Gram-positive signal peptide / LPXTG cell wall anchor motif / Gram-positive cocci surface proteins LPxTG motif profile. / Immunoglobulin / LPXTG cell wall anchor domain / Immunoglobulin domain / Neutral zinc metallopeptidases, zinc-binding region signature. / 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 / Immunoglobulin-like fold
Similarity search - Domain/homology
Immunoglobulin heavy constant alpha 1 / Immunoglobulin A1 protease
Similarity search - Component
Biological speciesStreptococcus pneumoniae (strain ATCC BAA-255 / R6) (bacteria) / Homo sapiens (human) / Human (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 4.0 Å
AuthorsEisenmesser EZ / 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: Nat Commun / Year: 2020
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
DepositionJun 23, 2020-
Header (metadata) releaseJan 20, 2021-
Map releaseJan 20, 2021-
UpdateJan 20, 2021-
Current statusJan 20, 2021Processing site: RCSB / Status: Released

-
Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.15
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by radius
  • Surface level: 0.15
  • Imaged by UCSF Chimera
  • Download
  • Surface view with fitted model
  • Atomic models: PDB-6xja
  • Surface level: 0.15
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_22204.png

Downloads & links

-
Map

FileDownload / File: emd_22204.map.gz / Format: CCP4 / Size: 42.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationIgA1 Protease with IgA1 substrate
Voxel sizeX=Y=Z: 1.59 Å
Density
Contour LevelBy AUTHOR: 0.15 / Movie #1: 0.15
Minimum - Maximum-0.4006242 - 0.75089216
Average (Standard dev.)0.00052375253 (±0.024103222)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions224224224
Spacing224224224
CellA=B=C: 356.15997 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.591.591.59
M x/y/z224224224
origin x/y/z0.0000.0000.000
length x/y/z356.160356.160356.160
α/β/γ90.00090.00090.000
start NX/NY/NZ000
NX/NY/NZ350350350
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS224224224
D min/max/mean-0.4010.7510.001

-
Supplemental data

-
Sample components

-
Entire : IgA1 Protease and IgA1 substrate

EntireName: IgA1 Protease and IgA1 substrate
Components
  • Complex: IgA1 Protease and IgA1 substrate
    • Complex: Immunoglobulin A1 protease
      • Protein or peptide: Immunoglobulin A1 protease
    • Complex: Immunoglobulin heavy constant alpha 1, Immunoglobulin alpha-1 light chain, Immunoglobulin alpha-1 heavy chain
      • Protein or peptide: Immunoglobulin heavy constant alpha 1
      • Protein or peptide: Immunoglobulin alpha-1 light chain
      • Protein or peptide: Immunoglobulin alpha-1 heavy chain

-
Supramolecule #1: IgA1 Protease and IgA1 substrate

SupramoleculeName: IgA1 Protease and IgA1 substrate / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Molecular weightTheoretical: 300 KDa

-
Supramolecule #2: Immunoglobulin A1 protease

SupramoleculeName: Immunoglobulin A1 protease / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1
Source (natural)Organism: Streptococcus pneumoniae (strain ATCC BAA-255 / R6) (bacteria)
Strain: ATCC BAA-255 / R6
Recombinant expressionOrganism: Escherichia coli (E. coli)

-
Supramolecule #3: Immunoglobulin heavy constant alpha 1, Immunoglobulin alpha-1 lig...

SupramoleculeName: 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
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Immunoglobulin A1 protease

MacromoleculeName: Immunoglobulin A1 protease / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: IgA-specific metalloendopeptidase
Source (natural)Organism: Streptococcus pneumoniae (strain ATCC BAA-255 / R6) (bacteria)
Strain: ATCC BAA-255 / R6
Molecular weightTheoretical: 145.926625 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: 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

MacromoleculeName: Immunoglobulin heavy constant alpha 1 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Human (human)
Molecular weightTheoretical: 22.887988 KDa
SequenceString: 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

MacromoleculeName: Immunoglobulin alpha-1 light chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Human (human)
Molecular weightTheoretical: 21.947256 KDa
SequenceString: 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

MacromoleculeName: Immunoglobulin alpha-1 heavy chain / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Human (human)
Molecular weightTheoretical: 21.93048 KDa
SequenceString: 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

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7 / Details: 20 mM Hepes, pH 7 150 mM NaCl
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: OTHER / Imaging mode: BRIGHT FIELDBright-field microscopy
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 30.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Initial angle assignmentType: OTHER
Final angle assignmentType: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 4.0 Å / Resolution method: FSC 3 SIGMA CUT-OFF / Number images used: 100000

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more