What does this research mean for the field?

A novel TR-FRET biosensor can quantify phosphorylation- and mutation-dependent structural changes in human cardiac myosin-binding protein C, revealing that phosphorylation increases the distance and disorder between the C1 and M-domains. Novelty: ClaimNovelty.METHODOLOGICAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

February 25, 2022Journal of Molecular and Cellular CardiologyOpen Access

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

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Why the study?

Mimicking the structural dynamics of phosphorylated cMyBP-C with small molecules could improve contractility in heart failure, motivating biosensors to monitor intramolecular structural changes from phosphorylation and mutations.

Population

Human cMyBP-C N-terminal domains C0 through C2 biosensor

Comparison

Phosphorylation and R282W mutation vs unphosphorylated or wild-type states

Design

In vitro structural biophysical assay using TR-FRET

Authors

RKRhye‐Samuel KanassategaUniversity of Arizona TBThomas A. BunchUniversity of Arizona VLVictoria C. LepakHeart Failure / Cardiomyopathy

Discussion

Member takes

Implication

Hypothesis-generating for cMyBP-C dynamics; extends biosensor screening platforms but requires validation before therapeutic translation.

Structured PICO

Population

Human cardiac myosin-binding protein C (cMyBP-C) biosensor model

Intervention

Phosphorylation and site-directed mutagenesis (including hypertrophic cardiomyopathy mutation R282W)

Comparator

Unphosphorylated or wild-type cMyBP-C

Outcome

Intramolecular structural changes measured by time-resolved fluorescence resonance energy transfer (TR-FRET) efficiencysurrogate

A novel TR-FRET biosensor successfully detects phosphorylation- and mutation-dependent structural changes in human cMyBP-C, providing a platform for high-throughput screening of heart failure therapeutics.

Cite This Study

Kanassatega et al. (2022) studied this question.

synapsesocial.com/papers/6a1be651ea84844e355f260c https://doi.org/10.1016/j.yjmcc.2022.02.005

Topics

HFrEF treatment Heart failure

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

Discussion

Member takes

Implication

Structured PICO

Cite This Study

Topics

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

Discussion

Member takes

Implication

Structured PICO

Cite This Study

Also Consider

Topics

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