You are here

Structural and Protein Interaction Effects of Hypertrophic and Dilated Cardiomyopathic Mutations in Alpha-Tropomyosin

Title: Structural and Protein Interaction Effects of Hypertrophic and Dilated Cardiomyopathic Mutations in Alpha-Tropomyosin.
44 views
7 downloads
Name(s): Pinto, Jose Renato, author
Chang, Audrey N., author
Greenfield, Norma J., author
Singh, Abhishek, author
Potter, James D., author
Type of Resource: text
Genre: Text
Date Issued: 2014-12-02
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: The potential alterations to structure and associations with thin filament proteins caused by the dilated cardiomyopathy (DCM) associated tropomyosin (Tm) mutants E40K and E54K, and the hypertrophic cardiomyopathy (HCM) associated Tm mutants E62Q and L185R, were investigated. In order to ascertain what the cause of the known functional effects may be, structural and protein-protein interaction studies were conducted utilizing actomyosin ATPase activity measurements and spectroscopy. In actomyosin ATPase measurements, both HCM mutants and the DCM mutant E54K caused increases in Ca2+-induced maximal ATPase activities, while E40K caused a decrease. Investigation of Tm's ability to inhibit actomyosin ATPase in the absence of troponin showed that HCM-associated mutant Tms did not inhibit as well as wildtype, whereas the DCM associated mutant E40K inhibited better. E54K did not inhibit the actomyosin ATPase activity at any concentration of Tm tested. Thermal denaturation studies by circular dichroism and molecular modeling of the mutations in Tm showed that in general, the DCM mutants caused localized destabilization of the Tm dimers, while the HCM mutants resulted in increased stability. These findings demonstrate that the structural alterations in Tm observed here may affect the regulatory function of Tm on actin, thereby directly altering the ATPase rates of myosin.
Identifier: FSU_libsubv1_scholarship_submission_1475067030 (IID), 10.3389/fphys.2014.00460 (DOI), PMC4251307 (PMCID)
Keywords: tropomyosin structure, cardiomyopathy, circular dichroism, thermal denaturation, actomyosin ATPase, molecular modeling
Publication Note: Publisher's Version Also Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4251307/
Preferred Citation: Chang, A. N., Greenfield, N. J., Singh, A., Potter, J. D., & Pinto, J. R. (2014). Structural and protein interaction effects of hypertrophic and dilated cardiomyopathic mutations in alpha-tropomyosin. Frontiers in physiology, 5
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_libsubv1_scholarship_submission_1475067030
Host Institution: FSU
Is Part Of: Frontiers in Psychology.
Issue: iss. 5, vol. 2014

Choose the citation style.
Pinto, J. R., Chang, A. N., Greenfield, N. J., Singh, A., & Potter, J. D. (2014). Structural and Protein Interaction Effects of Hypertrophic and Dilated Cardiomyopathic Mutations in Alpha-Tropomyosin. Frontiers In Psychology. Retrieved from http://purl.flvc.org/fsu/fd/FSU_libsubv1_scholarship_submission_1475067030