ArticlePloS one2007
The R403Q myosin mutation implicated in familial hypertrophic cardiomyopathy causes disorder at the actomyosin interface.
Article in PloS one, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 30 citations in OpenAlex.
- Allele-specific dysregulation of lipid and energy metabolism in early-stage hypertrophic cardiomyopathy.Journal of molecular and cellular cardiology plus · 2024Article
- Single-nucleus RNA/ATAC-seq in early-stage HCM models predicts SWI/SNF-activation in mutant-myocytes, and allele-specific differences in fibroblasts.bioRxiv : the preprint server for biology · 2024Article
- Current RNA strategies in treating cardiovascular diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Myofilament dysfunction in diastolic heart failure.Heart failure reviews · 2024Review
- Revisiting Diagnosis and Treatment of Hypertrophic Cardiomyopathy: Current Practice and Novel Perspectives.Journal of clinical medicine · 2023Review
- Clinical Genetic Testing for the Cardiomyopathies and Arrhythmias: A Systematic Framework for Establishing Clinical Validity and Addressing Genotypic and Phenotypic Heterogeneity.Frontiers in cardiovascular medicine · 2016Article
- Recent Advances in the Molecular Genetics of Familial Hypertrophic Cardiomyopathy in South Asian Descendants.Frontiers in physiology · 2016Review
- Faster cross-bridge detachment and increased tension cost in human hypertrophic cardiomyopathy with the R403Q MYH7 mutation.The Journal of physiology · 2014Article
- Cell-intrinsic functional effects of the α-cardiac myosin Arg-403-Gln mutation in familial hypertrophic cardiomyopathy.Biophysical journal · 2012Article
- Myosin-V as a mechanical sensor: an elastic network study.Biophysical journal · 2012Article
- Genetics of hypertrophic cardiomyopathy.Current opinion in cardiology · 2010Review
- Article
- Myosin isoform determines the conformational dynamics and cooperativity of actin filaments in the strongly bound actomyosin complex.Journal of molecular biology · 2010Article
- The myosin C-loop is an allosteric actin contact sensor in actomyosin.Biochemistry · 2009Article
- Energy metabolism in heart failure and remodelling.Cardiovascular research · 2009Review
- Functional effects of the hypertrophic cardiomyopathy R403Q mutation are different in an alpha- or beta-myosin heavy chain backbone.The Journal of biological chemistry · 2008Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundMutations in virtually all of the proteins comprising the cardiac muscle sarcomere have been implicated in causing Familial Hypertrophic Cardiomyopathy (FHC). Mutations in the beta-myosin heavy chain (MHC) remain among the most common causes of FHC, with the widely studied R403Q mutation resulting in an especially severe clinical prognosis. In vitro functional studies of cardiac myosin containing the R403Q mutation have revealed significant changes in enzymatic and mechanical properties compared to wild-type myosin. It has been proposed that these molecular changes must trigger events that ultimately lead to the clinical phenotype. PRINCIPAL
findingsHere we examine the structural consequences of the R403Q mutation in a recombinant smooth muscle myosin subfragment (S1), whose kinetic features have much in common with slow beta-MHC. We obtained three-dimensional reconstructions of wild-type and R403Q smooth muscle S1 bound to actin filaments in the presence (ADP) and absence (apo) of nucleotide by electron cryomicroscopy and image analysis. We observed that the mutant S1 was attached to actin at highly variable angles compared to wild-type reconstructions, suggesting a severe disruption of the actin-myosin interaction at the interface. SIGNIFICANCE: These results provide structural evidence that disarray at the molecular level may be linked to the histopathological myocyte disarray characteristic of the diseased state.
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