Michael A. Geeves
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View article: Direct measurement of mavacamten and deoxyATP perturbation of the SRX/DRX ratio in porcine cardiac myofibrils using a simple, accessible and multiplexed approach
Direct measurement of mavacamten and deoxyATP perturbation of the SRX/DRX ratio in porcine cardiac myofibrils using a simple, accessible and multiplexed approach Open
Cardiac muscle adapts to varying physiological demands by modulating the number of active myosin II motors available for contraction. These motors are organized into thick filaments in the sarcomere and generate force through an ATP-depend…
View article: Extracellular vesicle-linked vitamin B12 acquisition via novel binding proteins in <i>Bacteroides thetaiotaomicron</i>
Extracellular vesicle-linked vitamin B12 acquisition via novel binding proteins in <i>Bacteroides thetaiotaomicron</i> Open
Vitamin B12 (cobalamin) and related cobamides are essential cofactors for many gut bacteria, yet their acquisition requires complex uptake systems due to limited availability. In the human gut commensal Bacteroides thetaiotaomicron, cobami…
View article: Molecular mechanisms of altered contraction with the β-myosin R403Q mutation in porcine ventricular muscle and a human stem cell-derived cardiomyocyte model
Molecular mechanisms of altered contraction with the β-myosin R403Q mutation in porcine ventricular muscle and a human stem cell-derived cardiomyocyte model Open
I. ABSTRACT The R403Q mutation in the sarcomere protein beta-myosin heavy chain (β-MHC) is a known genetic cause of hypertrophic cardiomyopathy (HCM), associated with ventricular hypercontractility, impaired relaxation, and cardiac arrhyth…
View article: Extracellular Vesicle-Linked Vitamin B<sub>12</sub> Acquisition via Novel Binding Proteins in <i>Bacteroides thetaiotaomicron</i>
Extracellular Vesicle-Linked Vitamin B<sub>12</sub> Acquisition via Novel Binding Proteins in <i>Bacteroides thetaiotaomicron</i> Open
The acquisition and utilization of vitamin B 12 (cobalamin) are essential for the metabolic functions of many gut bacteria, including Bacteroides thetaiotaomicron , which relies on external sources of cobalamin due to its inability to synt…
View article: Direct measurement of mavacamten and deoxyATP perturbation of the SRX/DRX ratio in porcine cardiac myofibrils using a simple, accessible and multiplexed approach
Direct measurement of mavacamten and deoxyATP perturbation of the SRX/DRX ratio in porcine cardiac myofibrils using a simple, accessible and multiplexed approach Open
Cardiac muscle adapts to varying physiological demands by modulating the number of active myosin II motors available for contraction. These motors are organized into thick filaments in the sarcomere and generate force through an ATP-depend…
View article: Rapid changes in hydrostatic pressure as a probe for correlating function of purified proteins with their measured activity in living cells
Rapid changes in hydrostatic pressure as a probe for correlating function of purified proteins with their measured activity in living cells Open
Hydrostatic pressure (HP) has long been used to perturb protein and membrane structures and to alter their interactions with binding partners in a fully reversible manner. HP has also long been used to perturb molecular structures in livin…
View article: Spatially resolving how cMyBP-C phosphorylation and haploinsufficiency in porcine and human myofibrils affect β-cardiac myosin activity
Spatially resolving how cMyBP-C phosphorylation and haploinsufficiency in porcine and human myofibrils affect β-cardiac myosin activity Open
β-cardiac myosin mediates cardiac muscle contraction within the sarcomere by binding to the thin filament in an ATP-powered reaction. This process is highly regulated on a beat-to-beat basis by calcium interactions with the thin filament, …
View article: Conserved Phosphorylation of the Myosin1e <scp>TH1</scp> Domain Impacts Membrane Association and Function in Yeast and Worms
Conserved Phosphorylation of the Myosin1e <span>TH1</span> Domain Impacts Membrane Association and Function in Yeast and Worms Open
Cells have an intrinsic ability to rapidly respond to environmental change to regulate cell cycle progression and membrane organisation, thereby affecting cell growth and division. The actin cytoskeleton is a highly dynamic complex of prot…
View article: Molecular mechanisms of altered contraction with the β-myosin R403Q mutation in porcine ventricular muscle and a human stem cell-derived cardiomyocyte model
Molecular mechanisms of altered contraction with the β-myosin R403Q mutation in porcine ventricular muscle and a human stem cell-derived cardiomyocyte model Open
View article: Motor domain phosphorylation increases nucleotide exchange and turns MYO6 into a faster and stronger motor
Motor domain phosphorylation increases nucleotide exchange and turns MYO6 into a faster and stronger motor Open
View article: Spatially resolving how phosphorylation affects ß-cardiac myosin activity in porcine myofibril sarcomeres with single molecule resolution
Spatially resolving how phosphorylation affects ß-cardiac myosin activity in porcine myofibril sarcomeres with single molecule resolution Open
Cardiac muscle contraction is mediated by myosin binding from the thick filament of the sarcomere to the thin filament in an ATP powered reaction. This process is highly regulated on a beat-to-beat basis by calcium interactions with the th…
View article: An atomistic model of myosin interacting heads motif dynamics and their modification by 2’-deoxy-ADP
An atomistic model of myosin interacting heads motif dynamics and their modification by 2’-deoxy-ADP Open
The contraction of striated muscle is driven by cycling myosin motor proteins embedded within the thick filaments of sarcomeres. In addition to cross-bridge cycling with actin, these myosin proteins can enter an inactive, sequestered state…
View article: MYBPC3-c.772G>A mutation results in haploinsufficiency and altered myosin cycling kinetics in a patient induced stem cell derived cardiomyocyte model of hypertrophic cardiomyopathy
MYBPC3-c.772G>A mutation results in haploinsufficiency and altered myosin cycling kinetics in a patient induced stem cell derived cardiomyocyte model of hypertrophic cardiomyopathy Open
View article: Myosin’s powerstroke transitions define atomic scale movement of cardiac thin filament tropomyosin
Myosin’s powerstroke transitions define atomic scale movement of cardiac thin filament tropomyosin Open
Dynamic interactions between the myosin motor head on thick filaments and the actin molecular track on thin filaments drive the myosin-crossbridge cycle that powers muscle contraction. The process is initiated by Ca2+ and the opening of tr…
View article: The biochemically defined super relaxed state of myosin—A paradox
The biochemically defined super relaxed state of myosin—A paradox Open
View article: Danicamtiv Increases Myosin Recruitment and Alters Cross-Bridge Cycling in Cardiac Muscle
Danicamtiv Increases Myosin Recruitment and Alters Cross-Bridge Cycling in Cardiac Muscle Open
BACKGROUND: Modulating myosin function is a novel therapeutic approach in patients with cardiomyopathy. Danicamtiv is a novel myosin activator with promising preclinical data that is currently in clinical trials. While it is known that dan…
View article: Comparing the effects of chemical Ca2+ dyes and R-GECO on contractility and Ca2+ transients in adult and human iPSC cardiomyocytes
Comparing the effects of chemical Ca2+ dyes and R-GECO on contractility and Ca2+ transients in adult and human iPSC cardiomyocytes Open
View article: Distinct effects of two hearing loss–associated mutations in the sarcomeric myosin MYH7b
Distinct effects of two hearing loss–associated mutations in the sarcomeric myosin MYH7b Open
For decades, sarcomeric myosin heavy chain proteins were assumed to be restricted to striated muscle where they function as molecular motors that contract muscle. However, MYH7b, an evolutionarily ancient member of this myosin family, has …
View article: Effects of Hydrostatic-Pressure on Muscle Contraction: A Look Back on Some Experimental Findings
Effects of Hydrostatic-Pressure on Muscle Contraction: A Look Back on Some Experimental Findings Open
Findings from experiments that used hydrostatic pressure changes to analyse the process of skeletal muscle contraction are re-examined. The force in resting muscle is insensitive to an increase in hydrostatic pressure from 0.1 MPa (atmosph…
View article: Danicamtiv increases myosin recruitment and alters the chemomechanical cross bridge cycle in cardiac muscle
Danicamtiv increases myosin recruitment and alters the chemomechanical cross bridge cycle in cardiac muscle Open
Modulating myosin function is a novel therapeutic approach in patients with cardiomyopathy. Detailed mechanism of action of these agents can help predict potential unwanted affects and identify patient populations that can benefit most fro…
View article: Herbert (Freddie) Gutfreund. 21 October 1921—21 March 2021
Herbert (Freddie) Gutfreund. 21 October 1921—21 March 2021 Open
Herbert (Freddie) Gutfreund (hereafter called Freddie) made fundamental contributions to molecular enzymology—a name he introduced into the UK Biochemical Society as its first subgroup and as a discipline within the field of biochemistry. …
View article: Pseudo-phosphorylation of essential light chains affects the functioning of skeletal muscle myosin
Pseudo-phosphorylation of essential light chains affects the functioning of skeletal muscle myosin Open
View article: Single-molecule imaging reveals how mavacamten and PKA modulate ATP turnover in skeletal muscle myofibrils
Single-molecule imaging reveals how mavacamten and PKA modulate ATP turnover in skeletal muscle myofibrils Open
Muscle contraction is controlled at two levels: the thin and the thick filaments. The latter level of control involves three states of myosin heads: active, disordered relaxed (DRX), and super-relaxed (SRX), the distribution of which contr…
View article: Functional divergence of the sarcomeric myosin, MYH7b, supports species-specific biological roles
Functional divergence of the sarcomeric myosin, MYH7b, supports species-specific biological roles Open
View article: Acetylation stabilises calmodulin‐regulated calcium signalling
Acetylation stabilises calmodulin‐regulated calcium signalling Open
Calmodulin is a conserved calcium signalling protein that regulates a wide range of cellular functions. Amino‐terminal acetylation is a ubiquitous post‐translational modification that affects the majority of human proteins, to stabilise st…
View article: Exploring the super-relaxed state of myosin in myofibrils from fast-twitch, slow-twitch, and cardiac muscle
Exploring the super-relaxed state of myosin in myofibrils from fast-twitch, slow-twitch, and cardiac muscle Open
Muscle myosin heads, in the absence of actin, have been shown to exist in two states, the relaxed (turnover ∼0.05 s-1) and super-relaxed states (SRX, 0.005 s-1) using a simple fluorescent ATP chase assay (Hooijman, P.…
View article: Effect of Myosin Isoforms on Cardiac Muscle Twitch of Mice, Rats and Humans
Effect of Myosin Isoforms on Cardiac Muscle Twitch of Mice, Rats and Humans Open
To understand how pathology-induced changes in contractile protein isoforms modulate cardiac muscle function, it is necessary to quantify the temporal-mechanical properties of contractions that occur under various conditions. Pathological …
View article: Alpha and beta myosin isoforms and human atrial and ventricular contraction
Alpha and beta myosin isoforms and human atrial and ventricular contraction Open
View article: Identification of sequence changes in myosin II that adjust muscle contraction velocity
Identification of sequence changes in myosin II that adjust muscle contraction velocity Open
The speed of muscle contraction is related to body size; muscles in larger species contract at slower rates. Since contraction speed is a property of the myosin isoform expressed in a muscle, we investigated how sequence changes in a range…
View article: The effect of variable troponin C mutation thin filament incorporation on cardiac muscle twitch contractions
The effect of variable troponin C mutation thin filament incorporation on cardiac muscle twitch contractions Open