Review
Biochemistry & Molecular Biology
Paul Dowling, Stephen Gargan, Dieter Swandulla, Kay Ohlendieck
Summary: The loss of skeletal muscle mass and strength is the main cause of frailty syndrome, which is closely associated with sarcopenia in the elderly. Mass spectrometry-based proteomic surveys have improved our understanding of the molecular and cellular changes during muscle atrophy and age-related fiber-type shifting. Proteomic analysis suggests that contractile proteins can be used as markers of fiber-type transitions during aging.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Physiology
J. M. Chalovich, L. Zhu, D. Johnson
Summary: Striated muscle contraction is inhibited by several actin associated proteins, and the binding of Ca2+ can relieve this inhibition. Tropomyosin can be positioned in three different states on actin, which are associated with different functional states of the contractile system. Mutants of troponin can stabilize different states and provide tools for studying individual states. The C-terminal region of troponin T plays a unique role in limiting Ca2+ activation.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Elumalai Pavadai, Michael J. Rynkiewicz, Zeyu Yang, Ian R. Gould, Steven B. Marston, William Lehman
Summary: This study reveals the phosphorylation regulation mechanism of cardiac-specific tropomyosin by utilizing protein modeling and molecular dynamics simulation. The results suggest that phosphorylated residues may interact closely with tropomyosin and the N-lobe of TnC, thereby affecting cardiac muscle contraction and relaxation.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2022)
Article
Multidisciplinary Sciences
Elisabetta Brunello, Lorenzo Marcucci, Malcolm Irving, Luca Fusi
Summary: The contraction of skeletal muscle is initiated by an increase in intracellular calcium concentration, causing a change in the structure of actin-containing thin filaments that allows binding of myosin motors from the thick filaments. The release of folded motors is triggered by thick filament stress, suggesting a positive feedback loop. This study reveals the coordination of thin and thick filament activation mechanisms and the coupling of these mechanisms through positive feedback loops, achieving rapid cooperative activation of skeletal muscle.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Natalia A. Koubassova, Andrey K. Tsaturyan
Summary: Contraction of cardiac muscle is regulated by Ca2+ ions via regulatory proteins, troponin (Tn), and tropomyosin (Tpm) associated with the thin (actin) filaments in myocardial sarcomeres. Recent cryo-electron microscopy (cryo-EM) models of the complex allow one to study the dynamic and mechanical properties of the complex using molecular dynamics (MD). However, further refinement of the models is needed to improve the protein-protein interaction in some regions of the complex, as suggested by problems revealed from the MD simulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Allison B. Mason, Melissa L. Lynn, Anthony P. Baldo, Andrea E. Deranek, Jil C. Tardiff, Steven D. Schwartz
Summary: This study utilized computational modeling to predict and simulate the effects of mutations on cardiac thin filament proteins. Experimental validation was used to identify pathogenic signatures and reclassify variants, providing unique structural and dynamic information for classification of both new and conflicting variants.
Article
Biochemistry & Molecular Biology
Katarzyna Robaszkiewicz, Julia Wrobel, Joanna Moraczewska
Summary: Defects in maintaining the length of actin filaments may contribute to skeletal muscle diseases associated with mutations in tropomyosin genes. The p.R91C variant in Tpm3.12, a tropomyosin isoform expressed in slow-twitch muscle fibers, impairs the regulation of actin severing and depolymerization by cofilin-2, leading to abnormal actin filament turnover. Additionally, troponin also inhibits actin severing and depolymerization to some extent.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Physiology
Michael J. Rynkiewicz, Elumalai Pavadai, William Lehman
Summary: This article investigates the mechanism of calcium-dependent regulation of striated muscle contraction and reveals key intermolecular interactions and conformational changes through modeling and molecular dynamics simulation. It is of great significance for understanding mutation-induced contractile dysfunction related to muscle diseases.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Chemistry, Physical
Allison B. Mason, Jil C. Tardiff, Steven D. Schwartz
Summary: The interaction between cardiac troponin C (cTnC) and cardiac troponin I (cTnI) plays an important regulatory role in the contraction of cardiomyocytes. This study used metadynamics to calculate the free-energy surface of two transitions in the cardiac thin filament (CTF), and found that calcium ion stabilizes the open conformation of cTnC and that cTnC opening stabilizes the C-terminus of cTnI during its dissociation from actin.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Biochemistry & Molecular Biology
Kendal Prill, Michael R. Jones, Karl Steffensen, Grace Zi Teng, John F. Dawson
Summary: Many therapeutics for cardiomyopathy only alleviate symptoms without addressing the underlying mechanism. The onset of cardiomyopathy is believed to involve changes in calcium sensitivity and myosin activity. Trifluoperazine (TFP), a compound that binds troponin and other components of the calcium pathway, was studied to evaluate its impact on calcium regulation and heart function. In vitro experiments showed that TFP increased cardiac actomyosin activity while in vivo experiments using embryonic zebrafish demonstrated elevated heart rates with effective drug concentrations. In silico modeling suggested structural changes in troponin that could affect protein interactions within thin filaments and therefore impact heart function regulation.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Biology
Matthew H. Doran, William Lehman
Summary: Actin, a highly conserved protein, plays diverse roles in cellular processes by interacting with actin-binding proteins. The ATP-dependent cycle of myosin attachment and detachment drives muscle contraction and cellular transport. The variations in actin function are influenced by myosin isoforms and other actin-binding proteins.
Review
Biochemistry & Molecular Biology
Denis Noble
Summary: The 1968 review article accurately identified the major steps in muscle contraction and successfully identified the role of troponin, inspiring mathematical models of muscle activity to this day.
PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY
(2022)
Article
Biophysics
Larry S. Tobacman
Summary: Recent advances in understanding the structural basis of troponin-tropomyosin's regulation of striated muscle contraction, particularly through cryo-electron microscopy data, have revealed compelling atomic models for both apo- and Ca2+-saturated states. Subsequent analyses have further elucidated these findings, showing the hindering effects of troponin and tropomyosin on myosin-actin binding in relaxed muscle and the specific bindings in the Ca2+-saturated state.
BIOPHYSICAL JOURNAL
(2021)
Article
Multidisciplinary Sciences
Theresia Reindl, Sven Giese, Johannes N. Greve, Patrick Y. Reinke, Igor Chizhov, Sharissa L. Latham, Daniel P. Mulvihill, Manuel H. Taft, Dietmar J. Manstein
Summary: This article describes the effects of N-terminal acetylation of various tropomyosin isoforms on the actin affinity and thermal stability of actin-tropomyosin cofilaments. Additionally, it explores how the exchange of cytoskeletal tropomyosin isoforms and their acetylation impacts the kinetic and chemomechanical properties of cytoskeletal actin-tropomyosin-myosin complexes. The results highlight the extent of differences in kinetic and functional properties among different actin-tropomyosin-myosin complexes.
Article
Cell Biology
Daren Elkrief, Yu-Shu Cheng, Oleg S. Matusovsky, Dilson E. Rassier
Summary: The interaction between actin and myosin is crucial for muscle contraction and force production. Oxidation of actin and myosin has been found to weaken the myofibrils in healthy and diseased muscles. This study shows that exposure to a chemical compound can affect the interactions between actin and myosin, leading to decreased velocity and force. Oxidation of both actin and myosin contributes to a decrease in contractile activity in muscles.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Biophysics
Sam Walcott, David M. Warshaw, Edward P. Debold
BIOPHYSICAL JOURNAL
(2012)
Article
Cardiac & Cardiovascular Systems
Edward P. Debold, Walid Saber, Yaser Cheema, Carol S. Bookwalter, Kathleen M. Trybus, David M. Warshaw, Peter VanBuren
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2010)
Article
Sport Sciences
Edward P. Debold
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
(2012)
Article
Biophysics
EP Debold, JB Patlak, DM Warshaw
BIOPHYSICAL JOURNAL
(2005)
Article
Cell Biology
EP Debold, H Dave, RH Fitts
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2004)
Meeting Abstract
Biophysics
EP Debold, RH Fitts
BIOPHYSICAL JOURNAL
(2003)
Meeting Abstract
Biochemistry & Molecular Biology
EP Debold, RH Fitts
Meeting Abstract
Biophysics
EP Debold, JB Patlak, A Armstrong, S Beck, DM Warshaw
BIOPHYSICAL JOURNAL
(2005)
Meeting Abstract
Biophysics
EP Debold, AL Armstrong, AC Federico, JP Schmitt, CE Seidman, JG Seidman, DM Warshaw
BIOPHYSICAL JOURNAL
(2004)
Article
Sport Sciences
D Hendelman, K Miller, C Bagget, E Debold, P Freedson
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
(2000)