Evolution of a Metal-Binding Cluster in the NH2-Terminal Variable Region of Avian Fast Skeletal Muscle Troponin T: Functional Divergence on the Basis of Tolerance to Structural Drifting

Jin, Jian Ping; Samanez, Rafael A.

doi:10.1007/s002390010139

Cited by 17 publications

(28 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DNA sequence alignment demonstrated that the turkey and chicken cTnT genes are highly similar (Table II), which is consistent with their close evolutionary relationship (Fig. 1A) (48). The DNA sequence alignment of exon 8 and flanking regions of turkey and chicken cTnT cDNA demonstrate only one T to C transition at a wobble base in the exon 8 sequence (Fig.…”

Section: An Unusual Low Molecular Weight Ctnt Missing the Exon 8-encosupporting

confidence: 74%

Exon Skipping in Cardiac Troponin T of Turkeys with Inherited Dilated Cardiomyopathy

Biesiadecki¹,

Jin

2002

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Troponin T is a central component of the thin filament-associated troponin-tropomyosin system and plays an essential role in the Ca 2؉ regulation of striated muscle contraction. The importance of the structure and function of troponin T is evident in the regulated isoform expression during development and the point mutations resulting in familial hypertrophic and dilated cardiomyopathies. We report here that turkeys with inherited dilated cardiomyopathy and heart failure express an unusual low molecular weight cardiac troponin T missing 11 amino acids due to the splice out of the normally conserved exon 8-encoded segment. The deletion of a 9-bp segment from intron 7 of the turkey cardiac troponin T gene may be responsible for the weakened splicing of the downstream exon 8 during mRNA processing. The exclusion of the exon 8-encoded segment results in conformational changes in cardiac troponin T, an altered binding affinity for troponin I and tropomyosin, and an increased calcium sensitivity of the actomyosin ATPase. Expression of the exon 8-deleted cardiac troponin T prior to the development of cardiomyopathy in turkeys indicates a novel RNA splicing disease and provides evidence for the role of troponin T structure-function variation in myocardial pathogenesis and heart failure.

show abstract

Section: An Unusual Low Molecular Weight Ctnt Missing the Exon 8-encosupporting

confidence: 74%

Exon Skipping in Cardiac Troponin T of Turkeys with Inherited Dilated Cardiomyopathy

Biesiadecki¹,

Jin

2002

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…The turkey belongs to the avian order of Galliformes that also includes the domestic chicken (17). To obtain primer sequences appropriate for the cloning of turkey cardiac TnI cDNA, we first extended the published partial chicken cardiac TnI cDNA sequence (18) to full-length.…”

Section: Methodsmentioning

confidence: 99%

An R111C Polymorphism in Wild Turkey Cardiac Troponin I Accompanying the Dilated Cardiomyopathy-related Abnormal Splicing Variant of Cardiac Troponin T with Potentially Compensatory Effects

Biesiadecki

Schneider

et al. 2004

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Cardiac muscle contraction is regulated by Ca 2؉through the troponin complex consisting of three subunits: troponin C (TnC), troponin T (TnT), and troponin I (TnI). We reported previously that the abnormal splicing of cardiac TnT in turkeys with dilated cardiomyopathy resulted in a greater binding affinity to TnI. In the present study, we characterized a polymorphism of cardiac TnI in the heart of wild turkeys. cDNA cloning and sequencing of the novel turkey cardiac TnI revealed a single amino acid substitution, R111C. Arg 111 in avian cardiac TnI corresponds to a Lys in mammals. This residue is conserved in cardiac and skeletal muscle TnIs across the vertebrate phylum, implying a functional importance. In the partial crystal structure of cardiac troponin, this amino acid resides in an ␣-helix that directly contacts with TnT. Structural modeling indicates that the substitution of Cys for Arg or Lys at this position would not disrupt the global structure of troponin. To evaluate the functional significance of the different size and charge between the Arg and Cys side chains, protein-binding assays using purified turkey cardiac TnI expressed in Escherichia coli were performed. The results show that the R111C substitution lowered binding affinity to TnT, which is potentially compensatory to the increased TnI-binding affinity of the cardiomyopathyrelated cardiac TnT splicing variant. Therefore, the fixation of the cardiac TnI Cys 111 allele in the wild turkey population and the corresponding functional effect reflect an increased fitness value, suggesting a novel target for the treatment of TnT myopathies.

show abstract

“…Avian fsTnT gene has more complex alternative splicing patterns due to the additional alternative exons w, P1-7(x) and y in the N-terminal region (Smillie, Golosinska et al 1988; Miyazaki, Jozaki et al 1999; Jin and Samanez 2001). Correspondingly, two-dimensional electrophoresis study of chicken leg muscle protein detected more than 40 different fsTnT protein splice forms (Imai, Hirai et al 1986).…”

Section: Developmental Regulation Of Tnt Isoform Genes and Alternamentioning

confidence: 99%

TNNT1, TNNT2, and TNNT3: Isoform genes, regulation, and structure–function relationships

Wei

Jin

2016

Gene

177

133

View full text Add to dashboard Cite

Troponin T (TnT) is a central player in the calcium regulation of actin thin filament function and is essential for the contraction of striated muscles. Three homologous genes have evolved in vertebrates to encode three muscle type-specific TnT isoforms: TNNT1 for slow skeletal muscle TnT, TNNT2 for cardiac muscle TnT, and TNNT3 for fast skeletal muscle TnT. Alternative splicing and posttranslational modifications confer additional structural and functional variations of TnT during development and muscle adaptation to various physiological and pathological conditions. This review focuses on the TnT isoform genes and their molecular evolution, alternative splicing, developmental regulation, structure-function relationships of TnT proteins, posttranslational modifications, and myopathic mutations and abnormal splicing. The goal is to provide a concise summary of the current knowledge and some perspectives for future research and translational applications.

show abstract

Evolution of a Metal-Binding Cluster in the NH2-Terminal Variable Region of Avian Fast Skeletal Muscle Troponin T: Functional Divergence on the Basis of Tolerance to Structural Drifting

Cited by 17 publications

References 37 publications

Exon Skipping in Cardiac Troponin T of Turkeys with Inherited Dilated Cardiomyopathy

Exon Skipping in Cardiac Troponin T of Turkeys with Inherited Dilated Cardiomyopathy

An R111C Polymorphism in Wild Turkey Cardiac Troponin I Accompanying the Dilated Cardiomyopathy-related Abnormal Splicing Variant of Cardiac Troponin T with Potentially Compensatory Effects

TNNT1, TNNT2, and TNNT3: Isoform genes, regulation, and structure–function relationships

Contact Info

Product

Resources

About