Troponins, Intrinsic Disorder, and Cardiomyopathy
Document Type
Article
Publication Date
2016
Keywords
cardiac troponin, cardiomyopathy-related mutations, dilated cardiomyopathy, hypertrophic cardiomyopathy, intrinsically disordered protein, protein-protein interaction
Digital Object Identifier (DOI)
https://doi.org/10.1515/hsz-2015-0303
Abstract
Cardiac troponin is a dynamic complex of troponin C, troponin I, and troponin T (TnC, TnI, and TnT, respectively) found in the myocyte thin filament where it plays an essential role in cardiac muscle contraction. Mutations in troponin subunits are found in inherited cardiomyopathies, such as hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). The highly dynamic nature of human cardiac troponin and presence of numerous flexible linkers in its subunits suggest that understanding of structural and functional properties of this important complex can benefit from the consideration of the protein intrinsic disorder phenomenon. We show here that mutations causing decrease in the disorder score in TnI and TnT are significantly more abundant in HCM and DCM than mutations leading to the increase in the disorder score. Identification and annotation of intrinsically disordered regions in each of the troponin subunits conducted in this study can help in better understanding of the roles of intrinsic disorder in regulation of interactomes and posttranslational modifications of these proteins. These observations suggest that disease-causing mutations leading to a decrease in the local flexibility of troponins can trigger a whole plethora of functional changes in the heart.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
Biological Chemistry, v. 397, issue 8, p. 731-751
Scholar Commons Citation
Na, Insung; Kong, Min J.; Straight, Shelby; Pinto, Jose R.; and Uversky, Vladimir N., "Troponins, Intrinsic Disorder, and Cardiomyopathy" (2016). Molecular Medicine Faculty Publications. 360.
https://digitalcommons.usf.edu/mme_facpub/360
