Energy landscapes reveal the myopathic effects of tropomyosin mutations

• Published in: Archives of biochemistry and biophysics Vol. 564; pp. 89 - 99
• Main Authors: Orzechowski, Marek, Fischer, Stefan, Moore, Jeffrey R., Lehman, William, Farman, Gerrie P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.12.2014
• Subjects: Actin; Actin Cytoskeleton - chemistry; Actin Cytoskeleton - genetics; Actin Cytoskeleton - metabolism; Amino Acid Substitution; Calcium - chemistry; Calcium - metabolism; Cardiomyopathies; Cardiomyopathy; Genetic Diseases, Inborn; Humans; Muscle regulation; Mutation, Missense; Myosin; Signal Transduction - genetics; Tropomyosin; Tropomyosin - chemistry; Tropomyosin - genetics; Tropomyosin - metabolism; Muscle regulation; Actin; Tropomyosin; Cardiomyopathy; Myosin

[Display omitted] •Interaction energies between mutant tropomyosins and actin were calculated.•Missense mutations reset the switching mechanism controlling muscle contraction.•Mutations distort energy landscapes in ways that explain many phenotypic traits.•Outcomes of mutations can be predicted in s...