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TitleZebrafish as a model for cardiac disease; Cryo-EM structure of native cardiac thin filaments from Danio Rerio.
Journal, issue, pagesJ Muscle Res Cell Motil, Vol. 44, Issue 3, Page 179-192, Year 2023
Publish dateJul 22, 2023
AuthorsMarston Bradshaw / John M Squire / Edward Morris / Georgia Atkinson / Rebecca Richardson / Jon Lees / Massimo Caputo / Giulia M Bigotti / Danielle M Paul /
PubMed AbstractActin, tropomyosin and troponin, the proteins that comprise the contractile apparatus of the cardiac thin filament, are highly conserved across species. We have used cryo-EM to study the three- ...Actin, tropomyosin and troponin, the proteins that comprise the contractile apparatus of the cardiac thin filament, are highly conserved across species. We have used cryo-EM to study the three-dimensional structure of the zebrafish cardiac thin and actin filaments. With 70% of human genes having an obvious zebrafish orthologue, and conservation of 85% of disease-causing genes, zebrafish are a good animal model for the study of human disease. Our structure of the zebrafish thin filament reveals the molecular interactions between the constituent proteins, showing that the fundamental organisation of the complex is the same as that reported in the human reconstituted thin filament. A reconstruction of zebrafish cardiac F-actin demonstrates no deviations from human cardiac actin over an extended length of 14 actin subunits. Modelling zebrafish homology models into our maps enabled us to compare, in detail, the similarity with human models. The structural similarities of troponin-T in particular, a region known to contain a hypertrophic cardiomyopathy 'hotspot', confirm the suitability of zebrafish to study these disease-causing mutations.
External linksJ Muscle Res Cell Motil / PubMed:37480427 / PubMed Central
MethodsEM (single particle)
Resolution3.9 - 15.4 Å
Structure data

EMDB-15901: Cryo-EM map of Zebrafish (Danio rerio) Cardiac Thin Filament
Method: EM (single particle) / Resolution: 15.4 Å

17120

8ord

EMDB-17120, PDB-8ord:
Cryo-EM map of zebrafish cardiac F-actin
Method: EM (single particle) / Resolution: 3.9 Å

Chemicals

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM / Adenosine diphosphate

ChemComp-PO4:
PHOSPHATE ION / Phosphate

Source
  • danio rerio (zebrafish)
KeywordsCONTRACTILE PROTEIN / F-actin / Actin / Cardiac Actin / Filamentous

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