scholarly journals Tropomodulin: a cytoskeletal protein that binds to the end of erythrocyte tropomyosin and inhibits tropomyosin binding to actin.

1990 ◽  
Vol 111 (2) ◽  
pp. 471-481 ◽  
Author(s):  
V M Fowler
Keyword(s):  
Endothelial Cells ◽  
Actin Filament ◽  
Troponin I ◽  
Striated Muscle ◽  
Troponin T ◽  
Membrane Skeleton ◽  
Competitive Inhibitor ◽  
Cytoskeletal Protein ◽  
Apparent Affinity ◽  
Hill Plots

Human erythrocytes contain a Mr 43,000 tropomyosin-binding protein that is unrelated to actin and that has been proposed to play a role in modulating the association of tropomyosin with spectrin-actin complexes based on its stoichiometry in the membrane skeleton of one Mr 43,000 monomer per short actin filament (Fowler, V. M. 1987. J. Biol. Chem. 262:12792-12800). Here, we describe an improved procedure to purify milligram quantities to 98% homogeneity and we show that this protein inhibits tropomyosin binding to actin by a novel mechanism. We have named this protein tropomodulin. Unlike other proteins that inhibit tropomyosin-actin interactions, tropomodulin itself does not bind to F-actin. EM of rotary-shadowed tropomodulin-tropomyosin complexes reveal that tropomodulin (14.5 +/- 2.4 nm [SD] in diameter) binds to one of the ends of the rod-like tropomyosin molecules (33 nm long). In agreement with this observation, Dixon plots of inhibition curves demonstrate that tropomodulin is a non-competitive inhibitor of tropomyosin binding to F-actin (Ki = 0.7 microM). Hill plots of the binding of the tropomodulin-tropomyosin complex to actin indicate that binding does not exhibit any positive cooperativity (n = 0.9), in contrast to tropomyosin (n = 1.9), and that the apparent affinity of the complex for actin is reduced 20-fold with respect to that of tropomyosin. These results suggest that binding of tropomodulin to tropomyosin may block the ability of tropomyosin to self-associate in a head-to-tail fashion along the actin filament, thereby weakening its binding to actin. Antibodies to tropomodulin cross-react strongly with striated muscle troponin I (but not with troponin T) as well as with a nontroponin Mr 43,000 polypeptide in muscle and in other nonerythroid cells and tissues, including brain, lens, neutrophils, and endothelial cells. Thus, erythrocyte tropomodulin may be one member of a family of tropomyosin-binding proteins that function to regulate tropomyosin-actin interactions in non-muscle cells and tissues.

Functional and evolutionary relationships of troponin C

2007 ◽  
Vol 32 (1) ◽  
pp. 16-27 ◽  
Author(s):  
Todd E. Gillis ◽  
Christian R. Marshall ◽  
Glen F. Tibbits
Keyword(s):  
Functional Properties ◽  
Thin Filament ◽  
Troponin I ◽  
Striated Muscle ◽  
Troponin T ◽  
Extensive Study ◽  
Troponin C ◽  
High Conservation ◽  
Cross Bridges ◽  
And Function

Striated muscle contraction is initiated when, following membrane depolarization, Ca2+ binds to the low-affinity Ca2+ binding sites of troponin C (TnC). The Ca2+ activation of this protein results in a rearrangement of the components (troponin I, troponin T, and tropomyosin) of the thin filament, resulting in increased interaction between actin and myosin and the formation of cross bridges. The functional properties of this protein are therefore critical in determining the active properties of striated muscle. To date there are 61 known TnCs that have been cloned from 41 vertebrate and invertebrate species. In vertebrate species there are also distinct fast skeletal muscle and cardiac TnC proteins. While there is relatively high conservation of the amino acid sequence of TnC homologs between species and tissue types, there is wide variation in the functional properties of these proteins. To date there has been extensive study of the structure and function of this protein and how differences in these translate into the functional properties of muscles. The purpose of this work is to integrate these studies of TnC with phylogenetic analysis to investigate how changes in the sequence and function of this protein, integrate with the evolution of striated muscle.

scholarly journals Cardiac muscle thin filament structures reveal calcium regulatory mechanism

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Yurika Yamada ◽  
Keiichi Namba ◽  
Takashi Fujii
Keyword(s):  
Cardiac Muscle ◽  
Actin Filament ◽  
Conformational Changes ◽  
Thin Filament ◽  
Structural Changes ◽  
Troponin I ◽  
Regulatory Mechanism ◽  
Troponin T ◽  
Terminal Region ◽  
Muscle Thin Filament

AbstractContraction of striated muscles is driven by cyclic interactions of myosin head projecting from the thick filament with actin filament and is regulated by Ca2+ released from sarcoplasmic reticulum. Muscle thin filament consists of actin, tropomyosin and troponin, and Ca2+ binding to troponin triggers conformational changes of troponin and tropomyosin to allow actin-myosin interactions. However, the structural changes involved in this regulatory mechanism remain unknown. Here we report the structures of human cardiac muscle thin filament in the absence and presence of Ca2+ by electron cryomicroscopy. Molecular models in the two states built based on available crystal structures reveal the structures of a C-terminal region of troponin I and an N-terminal region of troponin T in complex with the head-to-tail junction of tropomyosin together with the troponin core on actin filament. Structural changes of the thin filament upon Ca2+ binding now reveal the mechanism of Ca2+ regulation of muscle contraction.

scholarly journals Troponin Variants as Markers of Skeletal Muscle Health and Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Monica Rasmussen ◽  
Jian-Ping Jin
Keyword(s):  
Skeletal Muscle ◽  
Troponin I ◽  
Striated Muscle ◽  
Troponin T ◽  
Muscle Quality ◽  
Striated Muscles ◽  
Thin Filaments ◽  
Age Related ◽  
Development And Aging ◽  
Regulation Of Muscle Contraction

Ca2+-regulated contractility is a key determinant of the quality of muscles. The sarcomeric myofilament proteins are essential players in the contraction of striated muscles. The troponin complex in the actin thin filaments plays a central role in the Ca2+-regulation of muscle contraction and relaxation. Among the three subunits of troponin, the Ca2+-binding subunit troponin C (TnC) is a member of the calmodulin super family whereas troponin I (TnI, the inhibitory subunit) and troponin T (TnT, the tropomyosin-binding and thin filament anchoring subunit) are striated muscle-specific regulatory proteins. Muscle type-specific isoforms of troponin subunits are expressed in fast and slow twitch fibers and are regulated during development and aging, and in adaptation to exercise or disuse. TnT also evolved with various alternative splice forms as an added capacity of muscle functional diversity. Mutations of troponin subunits cause myopathies. Owing to their physiological and pathological importance, troponin variants can be used as specific markers to define muscle quality. In this focused review, we will explore the use of troponin variants as markers for the fiber contents, developmental and differentiation states, contractile functions, and physiological or pathophysiological adaptations of skeletal muscle. As protein structure defines function, profile of troponin variants illustrates how changes at the myofilament level confer functional qualities at the fiber level. Moreover, understanding of the role of troponin modifications and mutants in determining muscle contractility in age-related decline of muscle function and in myopathies informs an approach to improve human health.

scholarly journals Sensitivity and specificity of cardiac troponin-T in diagnosis of acute myocardial infarction

2017 ◽  
Vol 4 (1) ◽  
pp. 244 ◽  
Author(s):  
Dharmveer Sharma ◽  
Poonam Gupta ◽  
Sagar Srivastava ◽  
Harshit Jain
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Striated Muscle ◽  
Troponin T ◽  
T Test ◽  
Specific Marker ◽  
Enzymatic Markers ◽  
Better Than

Background: Myocardial Infarction is the irreversible necrosis of the heart muscle secondary to prolong lack of oxygen supply. Troponin T is a structurally bound protein found in striated muscle cells. They have rapidly attained central role in diagnosis, prognostication and planning of therapeutic strategies in MI patients. The objective of this study was to evaluate the status of Troponin T in MI patients and its role in diagnosis compare to normal subjects.Methods: The study was conducted at M. L .N. Medical College, Allahabad, Uttar Pradesh India. A total of 136 cases were included in our study. Out of these, 86 were patients of AMI and 50 were healthy controls. They were evaluated by measurement of various parameters including enzymatic markers such as CPK-MB, SGOT, LDH1, and LDH2 and non-enzymatic markers such as troponin-T and myoglobin. Apart from these, LDL, VLDL and HDL levels were also kept under evaluation.Results: Troponin-T test was better than CPK-MB or SGOT in diagnosing myocardial infarction. In our study, sensitivity (67.3%) and specificity (73.8%) of troponin-T test was higher than CPK-MB (56.2% and 45.7%) and SGOT (34.2% and 58.3%) respectively. Troponin-T test was better than CPK-MB or SGOT after 2 hours of onset of myocardial infarction. Troponin- T and I: both kind of evaluations are available and are well evaluated. However troponin T estimation is more standardized and thus more popular. The positivity of troponin-T test also varied with area of infarct.Conclusions: High LDL and VLDL were seen while at the same time HDL level was lowered. An Increase in the level of myoglobin (non-specific marker), Cardiac troponin I and T and among the enzymatic markers elevated levels of CPK-MB, LDH and SGOT were observed in patients of MI against the normal subjects. In case of LDH both LDH 1 and LDH 2 were observed and a flipped pattern was noted. Bedside troponin-T test is highly sensitive and specific in the diagnosis of acute myocardial infarction and can be used in emergency and ambulatory settings. Qualitative troponin-T test is reliable above serum level of ≥ 0.10 ng/ml.

Acidic and basic troponin T isoforms in mature fast-twitch skeletal muscle and effect on contractility

1999 ◽  
Vol 276 (5) ◽  
pp. C1162-C1170 ◽  
Author(s):  
Ozgur Ogut ◽  
Henk Granzier ◽  
Jian-Ping Jin
Keyword(s):  
Troponin I ◽  
Striated Muscle ◽  
Troponin T ◽  
Muscle Fibers ◽  
Variable Region ◽  
Breast Muscle ◽  
Chicken Breast ◽  
Adult Chicken ◽  
Isoform Expression ◽  
Fast Twitch

Developmentally regulated alternative RNA splicing generates distinct classes of acidic and basic troponin T (TnT) isoforms. In fast-twitch skeletal muscles, an acidic-to-basic TnT isoform switch ensures basic isoform expression in the adult. As an exception, an acidic segment in the NH2-terminal variable region of adult chicken breast muscle TnT isoforms is responsible for the unique exclusive expression of acidic TnTs in this muscle (O. Ogut and J.-P. Jin. J. Biol. Chem. 273: 27858–27866, 1998). To understand the relationship between acidic vs. basic TnT isoform expression and muscle contraction, the contractile properties of fibers from adult chicken breast muscle were compared with those of the levator coccygeus muscle, which expresses solely basic TnT isoforms. With use of Triton X-100-skinned muscle fibers, the force and stiffness responses to Ca2+ were measured. Relative to the levator coccygeus muscle, the breast muscle fibers showed significantly increased sensitivity to Ca2+ of force and stiffness with a shift of ∼0.15 in the pCa at which force or stiffness was 50% of maximal. The expression of tropomyosin, troponin I, and troponin C isoforms was also determined to delineate their contribution to thin-filament regulation. The data indicate that TnT isoforms differing in their NH2-terminal charge are able to alter the sensitivity of the myofibrillar contractile apparatus to Ca2+. These results provide evidence linking the regulated expression of distinct acidic and basic TnT isoform classes to the contractility of striated muscle.

1461-P: Cardiac Troponin T and Troponin I and Incident Diabetes in the General Population: Generation Scotland Scottish Family Health Study

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1461-P
Author(s):  
PAUL WELSH ◽  
DAVID PREISS ◽  
ARCHIE CAMPBELL ◽  
DAVID J. PORTEOUS ◽  
NICHOLAS L. MILLS ◽  
...  
Keyword(s):  
General Population ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Troponin T ◽  
Family Health ◽  
Incident Diabetes ◽  
Health Study ◽  
Cardiac Troponin T ◽  
Generation Scotland

Postmortem Specificity of Troponin for Acute Miocard Infarction Diagnosis throug Qualitative Dosing from Pericardial Fluid

2018 ◽  
Vol 69 (9) ◽  
pp. 2482-2486
Author(s):  
Iuliana Hunea ◽  
Simona Irina Damian ◽  
Carmen Corina Radu ◽  
Sorin Moldoveanu ◽  
Tatiana Iov
Keyword(s):  
Sudden Cardiac Death ◽  
Cardiac Disease ◽  
Cardiac Death ◽  
Troponin I ◽  
Troponin T ◽  
Morphological Changes ◽  
Pericardial Fluid ◽  
Histological Changes ◽  
Lethal Arrhythmia ◽  
Myocardial Lesions

Cardiac disease is the leading cause of death, and sudden cardiac death occupies the first place in sudden deaths of natural causes. Sudden cardiac death due to lethal arrhythmia may be the first manifestation of a cardiac disease, such cases becoming suspect dead, thus forensic cases. The autopsy performed in such cases may reveal important cardiovascular disease but not obvious macroscopic or histological changes of acute myocardial infarction (IMA), except for cases of survival for several hours after the onset of the symptomatology. Biochemical markers were used to test for myocardial lesions in the absence of morphological changes. Methods for determining myoglobin, CK-MB, troponin T (cTn T), troponin I (cTn I) were introduced to the clinic to diagnose the condition of patients with chest pain as early as the 1990s. The lack of pathognomonic elements in corps investigations, where part of the analysis cannot be carried out, requires verification of the value of the investigations that can be carried out, with reference to the biochemical in the present case, in establishing the diagnosis with certainty.

scholarly journals The underestimated issue of non-reproducible cardiac troponin I and T results: case series and systematic review of the literature

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Julien Favresse ◽  
Jean-Louis Bayart ◽  
Damien Gruson ◽  
Sergio Bernardini ◽  
Aldo Clerico ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Judgment ◽  
Troponin I ◽  
Troponin T ◽  
Case Reports ◽  
False Negative ◽  
Case Series ◽  
Elevated Alkaline Phosphatase ◽  
Negative Results ◽  
Significant Difference

Abstract Cardiac troponins (cTn) are the preferred biomarkers for the evaluation of myocardial injury and play a key role in the diagnosis of acute myocardial infarction (MI). Pre-analytical or analytical issues and interferences affecting troponin T and I assays are therefore of major concern given the risk of misdiagnosis. False positive troponin results have been related to various interferences including anti-troponin antibodies, heterophilic antibodies, or elevated alkaline phosphatase level. On the other hand, false negative results have been reported in the case of a large biotin intake. These interferences are characterized with erroneous but reproducible troponin results. Of interest, non-reproducible results have also been reported in the literature. In other words, if the sample is reanalyzed a second time, a significant difference in troponin results will be observed. These interferences have been named “fliers” or “outliers”. Compared to the biotin interference that received major attention in the literature, troponin outliers are also able to induce harmful clinical consequences for the patient. Moreover, the prevalence of outliers in recent studies was found to be higher (0.28–0.57%) compared to the biotin interference. The aim of this systematic review is to warn clinicians about these non-reproducible results that may alter their clinical judgment. Four case reports that occurred in the Clinique of Saint-Luc Bouge are presented to attest this point. Moreover, we aimed at identifying the nature of these non-reproducible troponin results, determining their occurrence, and describing the best way for their identification.

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