Thomas A. Bunch

N-Terminal Actin-Binding Site of Lmod2 Promotes Controlled Pointed End Elongation

Tania M. Larrinaga, Garry E. Smith, Dmitri Tolkatchev, Timothy J. Rast et autres

BACKGROUND: Lmods (leiomodins) are critical for the assembly and maintenance of thin filaments in striated muscles by allowing thin filament elongation at the pointed ends. Lmod2's elongation function has been linked to both actin-binding sites (ABSs) 2 and 3, while the existence …

us (code pays fourni par la source)

BPS2026 – Targeting myosin-binding protein C by a high-throughput approach for cardiomyopathy therapeutics

Piyali Guhathakurta, Thomas A. Bunch, Andrew R. Thompson, Victoria C. Lepak et autres

us (code pays fourni par la source)

BPS2026 - Distinct structural dynamics between slow skeletal and cardiac myosin binding protein-C N-terminal domains

Morgan M. Seffrood, Thomas A. Bunch, Victoria C. Lepak, Brett A. Colson

BPS2026 – Cryo electron microscopy reveals the interaction of the cardiac myosin binding protein C N-terminal domains with the native cardiac thin filament

Cristina M. Risi, Tyler Nguyen, Thomas A. Bunch, Victoria C. Lepak et autres

us (code pays fourni par la source)

MYBPC3 N-terminal missense mutations linked to hypertrophic cardiomyopathy strengthen actin binding and enhance residue mobility

Rhye‐Samuel Kanassatega, Thomas A. Bunch, Fiona L. Wong, L. Michel Espinoza‐Fonseca et autres

Mutations in cardiac myosin-binding protein C (cMyBP-C) are a leading cause of hypertrophic cardiomyopathy (HCM). Although most cMyBP-C mutations produce truncated proteins and cause HCM via haploinsufficiency, the mechanisms by which missense mutations result in disease remain poorly understood. Here, we have …

us (code pays fourni par la source)

Cardiac myosin-binding protein C N-terminal interactions with myosin and actin filaments: Opposite effects of phosphorylation and M-domain mutations

Fiona L. Wong, Thomas A. Bunch, Victoria C. Lepak, Allison L. Steedman et autres

N-terminal cardiac myosin-binding protein C (cMyBP-C) domains (C0-C2) bind to thick (myosin) and thin (actin) filaments to coordinate contraction and relaxation of the heart. These interactions are regulated by phosphorylation of the M-domain situated between domains C1 and C2. In cardiomyopathies and …

us (code pays fourni par la source)

Drug discovery for heart failure targeting myosin-binding protein C

Thomas A. Bunch, Piyali Guhathakurta, Andrew R. Thompson, Victoria C. Lepak et autres

Cardiac MyBP-C (cMyBP-C) interacts with actin and myosin to fine-tune cardiac muscle contractility. Phosphorylation of cMyBP-C, which reduces the binding of cMyBP-C to actin and myosin, is often decreased in patients with heart failure (HF) and is cardioprotective in model systems of …

us (code pays fourni par la source)

Drug discovery for heart failure targeting myosin-binding protein C

Thomas A. Bunch, Piyali Guhathakurta, Andrew R. Thompson, Victoria C. Lepak et autres

Cardiac MyBP-C (cMyBP-C) interacts with actin-myosin to fine-tune cardiac muscle contractility. Phosphorylation of cMyBP-C, which reduces binding of cMyBP-C to actin or myosin, is often decreased in heart failure (HF) patients, and is cardioprotective in model systems for HF. Therefore, cMyBP-C is …

us (code pays fourni par la source)

Drug discovery for heart failure: Targeting the myosin-binding protein C interactions with actin

Piyali Guhathakurta, Thomas A. Bunch, Andrew Thompson, Victoria C. Lepak et autres

us (code pays fourni par la source)

Fluorescence lifetime-based assay reports structural changes in cardiac muscle mediated by effectors of contractile regulation

Alexey V. Dvornikov, Thomas A. Bunch, Victoria C. Lepak, Brett A. Colson

Cardiac muscle contraction is regulated by Ca2+-induced structural changes of the thin filaments to permit myosin cross-bridge cycling driven by ATP hydrolysis in the sarcomere. In congestive heart failure, contraction is weakened, and thus targeting the contractile proteins of the sarcomere is …

us (code pays fourni par la source)

N-terminal cardiac myosin-binding protein C interactions with myosin and actin filaments using time-resolved FRET

Fiona L. Wong, Thomas A. Bunch, Victoria C. Lepak, Brett A. Colson

Abstract Myosin binding protein-C (cMyBP-C) is a sarcomeric protein responsible for normal contraction and relaxation of the heart. We have used time-resolved fluorescence resonance energy transfer (TR-FRET) to resolve the interactions of cardiac myosin and F-actin with cMyBP-C, focusing on the N-terminal …

us (code pays fourni par la source)

Human cardiac myosin-binding protein C phosphorylation- and mutation-dependent structural dynamics monitored by time-resolved FRET

Rhye‐Samuel Kanassatega, Thomas A. Bunch, Victoria C. Lepak, Christopher Wang et autres

Cardiac myosin-binding protein C (cMyBP-C) is a thick filament-associated protein of the sarcomere and a potential therapeutic target for treating contractile dysfunction in heart failure. Mimicking the structural dynamics of phosphorylated cMyBP-C by small-molecule drug binding could lead to therapies that modulate …

us (code pays fourni par la source)