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

2001 ◽  
Vol 52 (2) ◽  
pp. 103-116 ◽  
Author(s):  
Jian-Ping Jin ◽  
Rafael A. Samanez
Keyword(s):  
Skeletal Muscle ◽  
Metal Binding ◽  
Troponin T ◽  
Functional Divergence ◽  
Variable Region ◽  
Fast Skeletal Muscle

scholarly journals Conformational modulation of slow skeletal muscle troponin T by an NH2-terminal metal-binding extension

2000 ◽  
Vol 279 (4) ◽  
pp. C1067-C1077 ◽  
Author(s):  
Jian-Ping Jin ◽  
Aihua Chen ◽  
Ozgur Ogut ◽  
Qi-Quan Huang
Keyword(s):  
Skeletal Muscle ◽  
Monoclonal Antibody ◽  
Metal Binding ◽  
Metal Ion ◽  
Troponin I ◽  
Troponin T ◽  
Terminal Region ◽  
Sequence Motif ◽  
Fast Skeletal Muscle ◽  
Slow Skeletal Muscle

Troponin T (TnT) is an essential element in the thin filament Ca2+-regulatory system controlling striated muscle contraction. Alternative RNA splicing generates developmental and muscle type-specific TnT isoforms differing in the hypervariable NH2-terminal region. Using avian fast skeletal muscle TnT containing a metal-binding segment, we have demonstrated a role of the NH2-terminal domain in modulating the conformation of TnT (Wang J and Jin JP. Biochemistry 37: 14519–14528, 1998). To further investigate the structure-function relationship of TnT, the present study constructed and characterized a recombinant protein in which the metal-binding peptide present in avian fast skeletal muscle TnT was fused to the NH2 terminus of mouse slow skeletal muscle TnT. Metal ion or monoclonal antibody binding to the NH2-terminal extension induced conformational changes in other domains of the model TnT molecule. This was shown by the altered affinity to a monoclonal antibody against the COOH-terminal region and a polyclonal antiserum recognizing multiple epitopes. Protein binding assays showed that metal binding to the NH2-terminal extension had effects on the interaction of TnT with troponin I, troponin C, and most significantly, tropomyosin. The data indicate that the NH2-terminal Tx [4–7 repeats of a sequence motif His-(Glu/Ala)-Glu-Ala-His] extension confers a specific conformational modulation in the slow skeletal muscle TnT.

The extent of amino-terminal heterogeneity in rabbit fast skeletal muscle troponin T

1987 ◽  
Vol 8 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Margaret M. Briggs ◽  
Jim J. -C. Lin ◽  
Frederick H. Schachat
Keyword(s):  
Skeletal Muscle ◽  
Troponin T ◽  
Fast Skeletal Muscle ◽  
Amino Terminal

scholarly journals CARDIAC TROPONIN T MEDIATED AUTOIMMUNE RESPONSE AND ITS ROLE IN SKELETAL MUSCLE AGING

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S882-S882
Author(s):  
Tan Zhang ◽  
Xin Feng ◽  
Bo Feng ◽  
Juan Dong ◽  
Karen Haas ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cardiac Troponin ◽  
Troponin T ◽  
Neuromuscular Diseases ◽  
Muscle Performance ◽  
Autoimmune Response ◽  
Cardiac Troponin T ◽  
Fast Skeletal Muscle ◽  
Age Related ◽  
Old Mice

Abstract Cardiac troponin T (cTnT), a key component of contractile machinery essential for muscle contraction, is also expressed in skeletal muscle under certain conditions (e.g. neuromuscular diseases and aging). We have reported that skeletal muscle cTnT regulates neuromuscular junction denervation preferentially in fast skeletal muscle of old mice. Here, we further report that cTnT is also enriched within some myofibers, and/or along microvascular walls in old mice fast skeletal muscle. Strikingly, immunoglobulin G (IgG), together with markers of complement system activation, cell death (necroptosis or apoptosis), and macrophage infiltration, were all found to be co-localized with cTnT and IgG in those areas. In addition, elevated cTnT and IgG are associated with lower dystrophin expression on muscle fiber membrane, lower muscle capillary density, and reduced muscle performance (wire hanging test). Using purified recombinant TnT proteins, we confirmed that only cTnT, but not slow or fast skeletal muscle TnT1 or TnT3, was detected by immunoblot using sera from old (but not young) mice with pre-determined elevated cTnT and IgG in their skeletal muscle, indicating the existence of anti-cTnT autoantibodies in sera (previously found in human blood) and skeletal muscle of old mice. Immunoblotting further revealed that the age related changes in skeletaI muscle cTnT and IgG are more prominent in fast skeletal muscle than in slow. Importantly, elevated cTnT and IgG were also detected in skeletal muscles from 4 older adults (65-70 yrs, IMFIT). Our finding suggests a novel autoimmune mechanism mediated by cTnT that underlies age related skeletal muscle abnormalities and dysfunction.

cDNA cloning and chromosomal mapping of mouse fast skeletal muscle troponin T

1997 ◽  
Vol 8 (5) ◽  
pp. 346-348 ◽  
Author(s):  
Anne Koch ◽  
Todd S. -C. Juan ◽  
Nancy A. Jenkins ◽  
Debra J. Gilbert ◽  
Neal G. Copeland ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cdna Cloning ◽  
Troponin T ◽  
Chromosomal Mapping ◽  
Fast Skeletal Muscle
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