+検索条件
-Structure paper
タイトル | Zebrafish as a model for cardiac disease; Cryo-EM structure of native cardiac thin filaments from Danio Rerio. |
---|---|
ジャーナル・号・ページ | J Muscle Res Cell Motil, Vol. 44, Issue 3, Page 179-192, Year 2023 |
掲載日 | 2023年7月22日 |
著者 | Marston Bradshaw / John M Squire / Edward Morris / Georgia Atkinson / Rebecca Richardson / Jon Lees / Massimo Caputo / Giulia M Bigotti / Danielle M Paul / |
PubMed 要旨 | 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- ...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. |
リンク | J Muscle Res Cell Motil / PubMed:37480427 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.9 - 15.4 Å |
構造データ | EMDB-15901: Cryo-EM map of Zebrafish (Danio rerio) Cardiac Thin Filament EMDB-17120, PDB-8ord: |
化合物 | ChemComp-ADP: ChemComp-PO4: |
由来 |
|
キーワード | CONTRACTILE PROTEIN / F-actin / Actin / Cardiac Actin / Filamentous |