Role of troponin T and AMP deaminase in the modulation of skeletal muscle contraction
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- 作者：Francesca Ronca ; Antonio Raggi
- 关键词：AMP deaminase ; Fast skeletal muscle ; Troponin T ; Calpain ; Zinc ; binding motif
- 刊名：Rendiconti Lincei
- 出版年：2017
- 出版时间：March 2017
- 年：2017
- 卷：28
- 期：1
- 页码：143-158
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- 刊物类别：Earth and Environmental Science
- 刊物主题：Environment, general; Earth Sciences, general; Life Sciences, general; Biomedicine, general; History of Science;
- 出版者：Springer International Publishing
- ISSN：1720-0776
- 卷排序：28
文摘
In fast muscle, isoforms of troponin T (TnT) contain an N-terminal hypervariable region that does not bind any protein of the thin filament. The N-terminal domain of TnT is removed by calpain during stress conditions and so could modulate the role of TnT in the regulation of contraction by affecting the TnT-binding affinity for tropomyosin (Tm) depending on the sequence and charge within the domain. During skeletal muscle contraction, the myokinase reaction is displaced by AMP deaminase (AMPD), an allosteric metalloenzyme, toward the formation of ATP. An unrestrained AMPD activity follows the proteolytic cleavage of the enzyme in vivo that releases a 97 aa N-terminal fragment, removing the inhibition exerted by the binding of ATP to a zinc site in the N-terminal region. Rabbit fast TnT or its phosphorylated 50-aa residue N-terminal peptide restores in AMPD the inhibition by ATP, removed in vitro by the release of a 95 aa N-terminal fragment by trypsin. Since the N-terminal region of fast rabbit TnT contains a putative zinc-binding motif, it can be inferred that TnT mimics the regulatory action exerted in native AMPD by the N-terminal domain that holds the enzyme in a less active conformation due to the presence of a zinc ion connecting the N-terminal and C-terminal regions. Together with evidence that AMPD is localized on the myofibril, the data reported in this review on the interactions between AMPD and TnT strongly suggest that these proteins mutually combine to fine-tune the regulation of muscle contraction in fast muscle.