[English] 日本語
Yorodumi
- PDB-9gvq: MUC5AC mucin amino acids 28 to 1483 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9gvq
TitleMUC5AC mucin amino acids 28 to 1483
ComponentsMucin-5AC
KeywordsPROTEIN FIBRIL / mucin / lung / filament / polymer / disulfide
Function / homology
Function and homology information


mucus layer / Defective GALNT3 causes HFTC / Defective C1GALT1C1 causes TNPS / Defective GALNT12 causes CRCS1 / Termination of O-glycan biosynthesis / O-linked glycosylation of mucins / extracellular matrix structural constituent / Dectin-2 family / extracellular matrix / Golgi lumen ...mucus layer / Defective GALNT3 causes HFTC / Defective C1GALT1C1 causes TNPS / Defective GALNT12 causes CRCS1 / Termination of O-glycan biosynthesis / O-linked glycosylation of mucins / extracellular matrix structural constituent / Dectin-2 family / extracellular matrix / Golgi lumen / extracellular space / extracellular exosome / metal ion binding / plasma membrane
Similarity search - Function
WxxW domain / Mucin-2 protein WxxW repeating region / : / C8 domain / Uncharacterised domain, cysteine-rich / C8 / von Willebrand factor, type D domain / von Willebrand factor type D domain / VWFD domain profile. / von Willebrand factor (vWF) type D domain ...WxxW domain / Mucin-2 protein WxxW repeating region / : / C8 domain / Uncharacterised domain, cysteine-rich / C8 / von Willebrand factor, type D domain / von Willebrand factor type D domain / VWFD domain profile. / von Willebrand factor (vWF) type D domain / C-terminal cystine knot signature. / von Willebrand factor (vWF) type C domain / Trypsin Inhibitor-like, cysteine rich domain / Serine protease inhibitor-like superfamily / Trypsin Inhibitor like cysteine rich domain / C-terminal cystine knot domain profile. / Cystine knot, C-terminal / C-terminal cystine knot-like domain (CTCK) / VWFC domain signature. / VWFC domain profile. / von Willebrand factor (vWF) type C domain / VWFC domain
Similarity search - Domain/homology
COPPER (II) ION / Mucin-5AC
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 3.9 Å
AuthorsHaberman, M. / Kamyshinsky, R. / Fass, D.
Funding supportEuropean Union, Israel, 2items
OrganizationGrant numberCountry
European Research Council (ERC)101097867European Union
Israel Science Foundation2660/20 Israel
CitationJournal: Proc Natl Acad Sci U S A / Year: 2025
Title: MUC5AC filaments illuminate the structural diversification of respiratory and intestinal mucins.
Authors: Meital Haberman / Roman Kamyshinsky / Nava Reznik / Noa Yeshaya / Lev Khmelnitsky / Elizabeth G Plender / Evan E Eichler / Deborah Fass /
Abstract: Secreted mucins are multimegadalton glycoprotein polymers that share the function of protecting mucosal tissues but diversified for activities in different organs of the body. Structural studies of ...Secreted mucins are multimegadalton glycoprotein polymers that share the function of protecting mucosal tissues but diversified for activities in different organs of the body. Structural studies of secreted mucins are complicated by the enormous sizes, flexibility, and complex supramolecular assembly modes of these glycoproteins. The two major respiratory mucins are MUC5AC and MUC5B. Here, we present structures of a large amino-terminal segment of MUC5AC in the form of helical filaments. These filaments differ from filamentous and tubular structures observed previously for the intestinal mucin MUC2 and the partial mucin homolog VWF. Nevertheless, the MUC5AC helical filaments support the proposed mechanism, based on MUC2 and VWF, for how noncovalent interactions between mucin monomers guide disulfide crosslinking to form polymers. The high-resolution MUC5AC structures show how local and limited changes in amino acid sequence can profoundly affect higher-order assembly while preserving the overall folds and polymerization activity of mucin glycoproteins. Differences in supramolecular assembly are likely to be functionally significant considering the divergence of mechanical properties and physiological requirements between respiratory and intestinal mucins. Determining the high-resolution structures of respiratory mucins provides a foundation for understanding the mechanisms by which they clean and protect the lungs. Moreover, the MUC5AC structure enables visualization of the sites of human amino acid sequence variation and disease-associated mutations.
History
DepositionSep 25, 2024Deposition site: PDBE / Processing site: PDBE
Revision 1.0Dec 4, 2024Provider: repository / Type: Initial release
Revision 1.1Mar 19, 2025Group: Data collection / Database references / Category: citation / citation_author / em_admin
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _citation_author.identifier_ORCID / _em_admin.last_update

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Mucin-5AC
B: Mucin-5AC
C: Mucin-5AC
D: Mucin-5AC
hetero molecules


Theoretical massNumber of molelcules
Total (without water)629,05820
Polymers628,3234
Non-polymers73516
Water00
1
A: Mucin-5AC
B: Mucin-5AC
C: Mucin-5AC
D: Mucin-5AC
hetero molecules

A: Mucin-5AC
B: Mucin-5AC
C: Mucin-5AC
D: Mucin-5AC
hetero molecules


Theoretical massNumber of molelcules
Total (without water)1,258,11640
Polymers1,256,6468
Non-polymers1,47032
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
point symmetry operation1

-
Components

#1: Protein
Mucin-5AC / MUC-5AC / Gastric mucin / Major airway glycoprotein / Mucin-5 subtype AC / tracheobronchial / ...MUC-5AC / Gastric mucin / Major airway glycoprotein / Mucin-5 subtype AC / tracheobronchial / Tracheobronchial mucin / TBM


Mass: 157080.688 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MUC5AC, MUC5 / Production host: Homo sapiens (human) / References: UniProt: P98088
#2: Chemical
ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 12 / Source method: obtained synthetically / Formula: Ca
#3: Chemical
ChemComp-CU / COPPER (II) ION


Mass: 63.546 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: Cu / Feature type: SUBJECT OF INVESTIGATION
Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: FILAMENT / 3D reconstruction method: helical reconstruction

-
Sample preparation

ComponentName: filament of the MUC5AC amino-terminal segment / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT
Molecular weightExperimental value: NO
Source (natural)Organism: Homo sapiens (human) / Cellular location: secreted / Tissue: lung
Source (recombinant)Organism: Homo sapiens (human) / Strain: HEK293F / Plasmid: pCDNA3.1
Buffer solutionpH: 5.2
Buffer component
IDConc.NameFormulaBuffer-ID
1100 mM2-(N-morpholino)ethanesulfonic acid1
21 Msodium chlorideNaCl1
310 mMcalcium chlorideCaCl21
445 micromolarzinc chloride1
SpecimenConc.: 0.45 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 295 K

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 1500 nm / Nominal defocus min: 600 nm
Image recordingElectron dose: 45 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

-
Processing

EM software
IDNameCategory
9PHENIXmodel refinement
10cryoSPARCinitial Euler assignment
11cryoSPARCfinal Euler assignment
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Helical symmertyAngular rotation/subunit: 74 ° / Axial rise/subunit: 94 Å / Axial symmetry: C1
3D reconstructionResolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 165735 / Symmetry type: HELICAL

+
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