D. D. Thomas

Kinetics and Mapping of Ca-driven Calmodulin conformations on Skeletal and Cardiac Muscle Ryanodine Receptors

The paper uses FRET to study CaM conformational changes on RyR in skeletal and cardiac muscle, finding CaM becomes more compact at high Ca2+ and showing isoform-specific differences.

Molecular Mechanism of a FRET Biosensor for the Cardiac Ryanodine Receptor Pathologically Leaky State

This paper uses FRET to study how DPc10 and CaM interact with RyR2, revealing their distinct effects on channel function and structural changes.

RyR2 Binding of an Antiarrhythmic Cyclic Depsipeptide Mapped Using Confocal Fluorescence Lifetime Detection of FRET

The paper maps the binding site of ent-verticilide on RyR2 using FRET and computational methods, identifying two potential loci within the RyR2 structure.

Cardiomyopathy-Associated Variants Alter the Structure and Function of the α-Actinin-2 Actin-Binding Domain

This study investigates how cardiomyopathy-associated variants in the α-actinin-2 actin-binding domain affect its structure and function, finding that some variants disrupt actin binding and may contribute to disease.

Allosteric coupling asymmetry mediates paradoxical activation of BRAF by type II inhibitors

The paper explains how type II RAF inhibitors paradoxically activate BRAF by inducing asymmetric dimerization, using biophysical and structural methods.

FRET assay for live-cell high-throughput screening of the cardiac SERCA pump yields multiple classes of small-molecule allosteric modulators

The paper uses a FRET assay to screen compounds affecting the cardiac SERCA pump, identifying activators and inhibitors with potential therapeutic applications for heart failure.

Identification of β-III-spectrin actin-binding modulators for treatment of spinocerebellar ataxia

The paper develops an in vitro FRET assay to identify small molecule modulators of the L253P mutant β-III-spectrin actin-binding domain, identifying potential drug candidates for SCA5 treatment.

High-throughput screen using fluorescence lifetime detects compounds that modulate myosin-binding protein C interactions with actin

This study identifies small-molecule inhibitors of actin-cMyBP-C binding using a fluorescence lifetime assay and validates their mechanism with complementary techniques.

Cardiac RyR N-terminal region biosensors for FRET-based high-throughput screening

This study develops FRET-based biosensors to screen for RyR modulators, identifying novel inhibitors and activators with therapeutic potential.

Super-relaxed state of myosin in human skeletal muscle is fiber-type dependent

This study measures the myosin super-relaxed state (SRX) in human skeletal muscle fibers, finding fiber-type dependent differences in SRX fraction and ATP turnover.

The transmembrane domain of DWORF activates SERCA directly; P15 and W22 residues are essential.

This study identifies key residues in DWORF that activate SERCA2a by displacing PLB, using FRET biosensors and mutagenesis.

Actin-binding compounds that affect the kinetics of the interaction of cardiac myosin with actin

This study examines ten actin-binding compounds' effects on cardiac myosin-actin interaction kinetics, revealing their impact on ATP affinity and potential therapeutic applications for hypertrophic cardiomyopathy.

Structural Basis for Allosteric Control of the SERCA-Phospholamban Membrane Complex by Ca2+ and cAMP-dependent Phosphorylation

This study reveals how phosphorylation and Ca2+ modulate the SERCA-PLN complex through structural changes that enhance Ca2+ transport.

Actin-binding compounds, discovered by FRET-based high-throughput screening, differentially affect skeletal and cardiac muscle

This study evaluates actin-binding compounds identified through TR-FRET screening, showing differential effects on skeletal and cardiac muscle actin and myofibril function.

Horse gluteus is a null-sarcolipin muscle with enhanced sarcoplasmic reticulum calcium transport

The paper analyzes Ca2+ regulation in horse gluteus muscle, finding high SLN RNA but low SLN protein, suggesting a non-coding role, and enhanced SR Ca2+ transport.

Viral expression of a SERCA2a-activating PLB mutant improves calcium cycling and synchronicity in dilated cardiomyopathic hiPSC-CMs

This paper demonstrates that expressing a PLB mutant in hiPSC-CMs improves calcium cycling and synchronicity in cardiomyopathy models.

Phospholamban and sarcolipin share similar transmembrane zipper motifs that control self-association affinity and oligomer stoichiometry

This study identifies conserved transmembrane zipper motifs in phospholamban and sarcolipin that regulate their self-association and oligomer stoichiometry through hydrophobic interactions.

Myosin Orientation in a Muscle Fiber Determined with High Angular Resolution Using Bifunctional Spin Labels

This study uses EPR with bifunctional spin labels to determine the orientation of myosin light chain domains in muscle fibers, finding lever arms perpendicular to the fiber axis under rigor conditions.

Age affects myosin relaxation states in skeletal muscle fibers of female but not male mice

This study finds that aging reduces myosin relaxation states (DRX and SRX) in female mice but not males, suggesting sex-specific effects on muscle aging.

Mavacamten stabilizes the auto-inhibited state of two-headed cardiac myosin

This paper investigates how mavacamten stabilizes the auto-inhibited state of two-headed cardiac myosin through biochemical and structural kinetics.

A dynamic mechanism for allosteric activation of Aurora kinase A by activation loop phosphorylation

This study shows that phosphorylation of Aurora A's activation loop activates the kinase without shifting the DFG-In state population, and that a DFG-Out subpopulation is important for optimized substrate binding kinetics.