scholarly journals Anomalous structural dynamics of minimally frustrated residues in cardiac troponin C triggers hypertrophic cardiomyopathy

2021 ◽  
Author(s):  
Mayra A. Marques ◽  
Maicon Landim-Vieira ◽  
Adolfo H. Moraes ◽  
Bin Sun ◽  
Jamie R. Johnston ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Structural Dynamics ◽  
Genetic Variants ◽  
Cardiac Troponin ◽  
Myocardial Contraction ◽  
Troponin C ◽  
Cardiac Troponin C

Cardiac TnC (cTnC) is highly conserved among mammals, and genetic variants can result in disease by perturbing Ca2+-regulation of myocardial contraction.

scholarly journals Hypertrophic Cardiomyopathy Cardiac Troponin C Mutations Differentially Affect Slow Skeletal and Cardiac Muscle Regulation

2017 ◽  
Vol 8 ◽  
Author(s):  
Tiago Veltri ◽  
Maicon Landim-Vieira ◽  
Michelle S. Parvatiyar ◽  
David Gonzalez-Martinez ◽  
Karissa M. Dieseldorff Jones ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Cardiac Muscle ◽  
Cardiac Troponin ◽  
Troponin C ◽  
Muscle Regulation ◽  
Cardiac Troponin C ◽  
Cardiac Muscle Regulation

scholarly journals A Mutation inTNNC1-encoded Cardiac Troponin C, TNNC1-A31S, Predisposes to Hypertrophic Cardiomyopathy and Ventricular Fibrillation

2012 ◽  
Vol 287 (38) ◽  
pp. 31845-31855 ◽  
Author(s):  
Michelle S. Parvatiyar ◽  
Andrew P. Landstrom ◽  
Cicero Figueiredo-Freitas ◽  
James D. Potter ◽  
Michael J. Ackerman ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Ventricular Fibrillation ◽  
Cardiac Troponin ◽  
Troponin C ◽  
Cardiac Troponin C

scholarly journals A Novel Mutation in TNNC1-ENCODED Cardiac Troponin C Predisposes to Hypertrophic Cardiomyopathy and Recurrent Episodes of Aborted Sudden Cardiac Death

2011 ◽  
Vol 100 (3) ◽  
pp. 114a
Author(s):  
Michelle S. Parvatiyar ◽  
Andrew P. Landstrom ◽  
Jose Renato Pinto ◽  
Jingsheng Liang ◽  
Michael J. Ackerman ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Sudden Cardiac Death ◽  
Cardiac Troponin ◽  
Cardiac Death ◽  
Novel Mutation ◽  
Troponin C ◽  
Cardiac Troponin C

A comprehensive guide to genetic variants and post-translational modifications of cardiac troponin C

2020 ◽  
Author(s):  
Tyler R. Reinoso ◽  
Maicon Landim-Vieira ◽  
Yun Shi ◽  
Jamie R. Johnston ◽  
P. Bryant Chase ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Cardiac Troponin ◽  
Troponin C ◽  
Post Translational Modifications ◽  
Cardiac Troponin C

Familial hypertrophic cardiomyopathy-related cardiac troponin C mutation L29Q affects Ca2+ binding and myofilament contractility

2008 ◽  
Vol 33 (2) ◽  
pp. 257-266 ◽  
Author(s):  
Bo Liang ◽  
Franca Chung ◽  
Yang Qu ◽  
Dmitri Pavlov ◽  
Todd E. Gillis ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Cardiac Myocytes ◽  
Cardiac Troponin ◽  
Sarcomere Length ◽  
Troponin C ◽  
Familial Hypertrophic Cardiomyopathy ◽  
Force Generation ◽  
Binding Characteristics ◽  
Cardiac Troponin C ◽  
Myocyte Contractility

The cardiac troponin C (cTnC) mutation, L29Q, has been found in a patient with familial hypertrophic cardiomyopathy. We previously showed that L29, together with neighboring residues, Asp2, Val28, and Gly30, plays an important role in determining the Ca2+ affinity of site II, the regulatory site of mammalian cardiac troponin C (McTnC). Here we report on the Ca2+ binding characteristics of L29Q McTnC and D2N/V28I/L29Q/G30D McTnC (NIQD) utilizing the Phe27 → Trp (F27W) substitution, allowing one to monitor Ca2+ binding and release. We also studied the effect of these mutants on Ca2+ activation of force generation in single mouse cardiac myocytes using cTnC replacement, together with sarcomere length (SL) dependence. The Ca2+-binding affinity of site II of L29Q McTnCF27W and NIQD McTnCF27W was ∼1.3- and ∼1.9-fold higher, respectively, than that of McTnCF27W. The Ca2+ disassociation rate from site II of L29Q McTnCF27W and NIQD McTnCF27W was not significantly different than that of control (McTnCF27W). However, the rate of Ca2+ binding to site II was higher in L29Q McTnCF27W and NIQD McTnCF27W relative to control (∼1.5-fold and ∼2.0-fold respectively). The Ca2+ sensitivity of force generation was significantly higher in myocytes reconstituted with L29Q McTnC (∼1.4-fold) and NIQD McTnC (∼2-fold) compared with those reconstituted with McTnC. Interestingly, the change in Ca2+ sensitivity of force generation in response to an SL change (1.9, 2.1, and 2.3 μm) was significantly reduced in myocytes containing L29Q McTnC or NIQD McTnC. These results demonstrate that the L29Q mutation enhances the Ca2+-binding characteristics of cTnC and that when incorporated into cardiac myocytes, this mutant alters myocyte contractility.

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