troponin complex
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2021 ◽  
Vol 22 (17) ◽  
pp. 9187
Author(s):  
Martijn van de Locht ◽  
Tamara C. Borsboom ◽  
Josine M. Winter ◽  
Coen A. C. Ottenheijm

The troponin complex is a key regulator of muscle contraction. Multiple variants in skeletal troponin encoding genes result in congenital myopathies. TNNC2 has been implicated in a novel congenital myopathy, TNNI2 and TNNT3 in distal arthrogryposis (DA), and TNNT1 and TNNT3 in nemaline myopathy (NEM). Variants in skeletal troponin encoding genes compromise sarcomere function, e.g., by altering the Ca2+ sensitivity of force or by inducing atrophy. Several potential therapeutic strategies are available to counter the effects of variants, such as troponin activators, introduction of wild-type protein through AAV gene therapy, and myosin modulation to improve muscle contraction. The mechanisms underlying the pathophysiological effects of the variants in skeletal troponin encoding genes are incompletely understood. Furthermore, limited knowledge is available on the structure of skeletal troponin. This review focusses on the physiology of slow and fast skeletal troponin and the pathophysiology of reported variants in skeletal troponin encoding genes. A better understanding of the pathophysiological effects of these variants, together with enhanced knowledge regarding the structure of slow and fast skeletal troponin, will direct the development of treatment strategies.


2021 ◽  
Vol 22 (8) ◽  
pp. 4036
Author(s):  
Małgorzata Śliwinska ◽  
Katarzyna Robaszkiewicz ◽  
Piotr Wasąg ◽  
Joanna Moraczewska

Tropomyosin is a two-chain coiled coil protein, which together with the troponin complex controls interactions of actin with myosin in a Ca2+-dependent manner. In fast skeletal muscle, the contractile actin filaments are regulated by tropomyosin isoforms Tpm1.1 and Tpm2.2, which form homo- and heterodimers. Mutations in the TPM2 gene encoding isoform Tpm2.2 are linked to distal arthrogryposis and congenital myopathy—skeletal muscle diseases characterized by hyper- and hypocontractile phenotypes, respectively. In this work, in vitro functional assays were used to elucidate the molecular mechanisms of mutations Q93H and E97K in TPM2. Both mutations tended to decrease actin affinity of homo-and heterodimers in the absence and presence of troponin and Ca2+, although the effect of Q93H was stronger. Changes in susceptibility of tropomyosin to trypsin digestion suggested that the mutations diversified dynamics of tropomyosin homo- and heterodimers on the filament. The presence of Q93H in homo- and heterodimers strongly decreased activation of the actomyosin ATPase and reduced sensitivity of the thin filament to [Ca2+]. In contrast, the presence of E97K caused hyperactivation of the ATPase and increased sensitivity to [Ca2+]. In conclusion, the hypo- and hypercontractile phenotypes associated with mutations Q93H and E97K in Tpm2.2 are caused by defects in Ca2+-dependent regulation of actin–myosin interactions.


2021 ◽  
Vol 118 (13) ◽  
pp. e2024288118
Author(s):  
Cristina M. Risi ◽  
Ian Pepper ◽  
Betty Belknap ◽  
Maicon Landim-Vieira ◽  
Howard D. White ◽  
...  

Every heartbeat relies on cyclical interactions between myosin thick and actin thin filaments orchestrated by rising and falling Ca2+ levels. Thin filaments are comprised of two actin strands, each harboring equally separated troponin complexes, which bind Ca2+ to move tropomyosin cables away from the myosin binding sites and, thus, activate systolic contraction. Recently, structures of thin filaments obtained at low (pCa ∼9) or high (pCa ∼3) Ca2+ levels revealed the transition between the Ca2+-free and Ca2+-bound states. However, in working cardiac muscle, Ca2+ levels fluctuate at intermediate values between pCa ∼6 and pCa ∼7. The structure of the thin filament at physiological Ca2+ levels is unknown. We used cryoelectron microscopy and statistical analysis to reveal the structure of the cardiac thin filament at systolic pCa = 5.8. We show that the two strands of the thin filament consist of a mixture of regulatory units, which are composed of Ca2+-free, Ca2+-bound, or mixed (e.g., Ca2+ free on one side and Ca2+ bound on the other side) troponin complexes. We traced troponin complex conformations along and across individual thin filaments to directly determine the structural composition of the cardiac native thin filament at systolic Ca2+ levels. We demonstrate that the two thin filament strands are activated stochastically with short-range cooperativity evident only on one of the two strands. Our findings suggest a mechanism by which cardiac muscle is regulated by narrow range Ca2+ fluctuations.


Food Industry ◽  
2020 ◽  
Vol 5 (1) ◽  
pp. 65-70
Author(s):  
Oksana Tabakaeva ◽  
Anton Tabakaev

Bivalve mollusk are protein raw materials, their soft tissues are characterized by a hard-rubbery consistency due to its proteins characteristics and should be considered when processing into food. The proteins fractional composition study of different groups (water-soluble, myofibrillar, and stroma) is an urgent task, since it is possible to justify the processing technology based on the obtained data. The article presents the fractional composition study results of the water-soluble proteins and peptides, the molecular mass distribution of the separate components of myofibrillary proteins and muscle tissue stroma proteins of the Mactra Chinensis mollusk motor muscle. The researchers noted that the total amount of the high-molecular fraction (molecular weight above 10 kDa) is 62.16 %, and the total peptide fraction amount (molecular weight below 10 kDa) is 37.84 %. There are four main components in myofibrillar proteins – myosin, actin, troponin complex components, and collagen. The content of the main myofibrillar protein that is myosin of various polymerization degrees of is 69.3 %; heavy myosin chains – 30.5 % of the total myofibrillar proteins content and 44.0 % of the relative content of the total myosin content; light myosin chains – 38.8 % of the total myofibrillar proteins content and 56.0 % of the relative content of the total myosin content. The authors determined that actin (molecular weight 43 kDa) and troponin complex components (molecular weight from 15 to 30 kDa) are approximately equal in content. The collagen content (molecular weight more than 300 kDa) in the myofibrillar fraction is only 8.2 %. Stroma proteins are represented by two main fractions with molecular weights of more than 250 and 500 kDa. Collagen is the predominant stroma protein, its content account for 62.6 %. There is a high connectin content in stroma proteins.


2019 ◽  
Vol 116 (33) ◽  
pp. 16384-16393 ◽  
Author(s):  
Oleg S. Matusovsky ◽  
Alf Mansson ◽  
Malin Persson ◽  
Yu-Shu Cheng ◽  
Dilson E. Rassier

High-speed atomic force microscopy (HS-AFM) can be used to study dynamic processes with real-time imaging of molecules within 1- to 5-nm spatial resolution. In the current study, we evaluated the 3-state model of activation of cardiac thin filaments (cTFs) isolated as a complex and deposited on a mica-supported lipid bilayer. We studied this complex for dynamic conformational changes 1) at low and high [Ca2+] (pCa 9.0 and 4.5), and 2) upon myosin binding to the cTF in the nucleotide-free state or in the presence of ATP. HS-AFM was used to directly visualize the tropomyosin–troponin complex and Ca2+-induced tropomyosin movements accompanied by structural transitions of actin monomers within cTFs. Our data show that cTFs at relaxing or activating conditions are not ultimately in a blocked or activated state, respectively, but rather the combination of states with a prevalence that is dependent on the [Ca2+] and the presence of weakly or strongly bound myosin. The weakly and strongly bound myosin induce similar changes in the structure of cTFs as confirmed by the local dynamical displacement of individual tropomyosin strands in the center of a regulatory unit of cTF at the relaxed and activation conditions. The displacement of tropomyosin at the relaxed conditions had never been visualized directly and explains the ability of myosin binding to TF at the relaxed conditions. Based on the ratios of nonactivated and activated segments within cTFs, we proposed a mechanism of tropomyosin switching from different states that includes both weakly and strongly bound myosin.


2019 ◽  
Vol 65 (7) ◽  
pp. 882-892 ◽  
Author(s):  
Alexandra V Vylegzhanina ◽  
Alexander E Kogan ◽  
Ivan A Katrukha ◽  
Ekaterina V Koshkina ◽  
Anastasia V Bereznikova ◽  
...  

AbstractBACKGROUNDThe measurement of cardiac isoforms of troponin I (cTnI) and troponin T (cTnT) is widely used for the diagnosis of acute myocardial infarction (AMI). However, there are conflicting data regarding what forms of cTnI and cTnT are present in the blood of AMI patients. We investigated cTnI and cTnT as components of troponin complexes in the blood of AMI patients.METHODSGel filtration techniques, sandwich fluoroimmunoassays, and Western blotting were used.RESULTSPlasma samples from patients with AMI contained the following troponin complexes: (a) a cTnI-cTnT-TnC complex (ITC) composed of full-size cTnT of 37 kDa or its 29-kDa fragment and full-size cTnI of 29 kDa or its 27-kDa fragments; (b) ITC with lower molecular weight (LMW-ITC) in which cTnT was truncated to the 14-kDa C-terminal fragments; and (c) a binary cTnI-cTnC complex composed of truncated cTnI of approximately 14 kDa. During the progression of the disease, the amount of ITC in AMI samples decreased, whereas the amounts of LMW-ITC and short 16- to 20-kDa cTnT central fragments increased. Almost all full-size cTnT and a 29-kDa cTnT fragment in AMI plasma samples were the components of ITC. No free full-size cTnT was found in AMI plasma samples. Only 16- to 27-kDa central fragments of cTnT were present in a free form in patient blood.CONCLUSIONSA ternary troponin complex exists in 2 forms in the blood of patients with AMI: full-size ITC and LMW-ITC. The binary cTnI-cTnC complex and free cTnT fragments are also present in patient blood.


Sensor Review ◽  
2018 ◽  
Vol 38 (1) ◽  
pp. 9-12
Author(s):  
Dejan Petrovic

Purpose The purpose of the paper is to analyze the ventricular tachycardia by soft computing. Ventricular tachycardia is a type of regular and fast heart rate which arises from improper electrical activity in the ventricles of the heart. Design/methodology/approach In this study, a soft computing approach was applied for the ventricular tachycardia detection. The soft computing was used to detect which factors are the most important for the ventricular tachycardia. Findings Three factors were used: brain natriuretic peptide, troponin I which is a part of the troponin complex and C-reactive protein which is an annular (ring-shaped), pentameric protein found in blood plasma. Originality/value It was found that troponin I has the most influence on the ventricular tachycardia prediction.


2018 ◽  
Vol 29 (11) ◽  
Author(s):  
Kisang Kwon ◽  
Bo Kyung Yoo ◽  
Younghwa Ko ◽  
Ji Young Choi ◽  
O Yu Kwon ◽  
...  

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