PUBLICATION
Zebrafish as a model for cardiac disease; Cryo-EM structure of native cardiac thin filaments from Danio Rerio
- Authors
- Bradshaw, M., Squire, J.M., Morris, E., Atkinson, G., Richardson, R., Lees, J., Caputo, M., Bigotti, G.M., Paul, D.M.
- ID
- ZDB-PUB-230723-43
- Date
- 2023
- Source
- Journal of muscle research and cell motility 44(3): 179-192 (Journal)
- Registered Authors
- Richardson, Rebecca
- Keywords
- Actin, Cryo-EM, Thin filament, Tropomyosin, Troponin, Zebrafish
- MeSH Terms
-
- Actin Cytoskeleton/metabolism
- Actins/metabolism
- Animals
- Calcium/metabolism
- Cardiomyopathy, Hypertrophic*/genetics
- Cryoelectron Microscopy
- Humans
- Tropomyosin/genetics
- Zebrafish*/metabolism
- PubMed
- 37480427 Full text @ J. Muscle Res. Cell Motil.
Citation
Bradshaw, M., Squire, J.M., Morris, E., Atkinson, G., Richardson, R., Lees, J., Caputo, M., Bigotti, G.M., Paul, D.M. (2023) Zebrafish as a model for cardiac disease; Cryo-EM structure of native cardiac thin filaments from Danio Rerio. Journal of muscle research and cell motility. 44(3):179-192.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping