What does this research mean for the field?

Phosphorylation and familial hypertrophic cardiomyopathy (FHC) mutations in the inhibitory and switch regions of cardiac troponin I significantly destabilize its interaction with troponin C, with specific FHC mutations either enhancing or suppressing the effects of phosphorylation. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.SUPPORTS_CONSENSUS.

November 15, 2003Biochemistry

Phosphorylation and Mutation of Human Cardiac Troponin I Deferentially Destabilize the Interaction of the Functional Regions of Troponin I with Troponin C,

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Population

Human cardiac troponin I (cTnI) segments (cRp, cIp, cSp) and troponin C (cTnC)

Comparison

Phosphorylation and familial hypertrophic… vs Native (unphosphorylated, unmutated) state

Design

Preclinical

Authors

MLMonica X. LiUniversity of Alberta XWXu WangJiangsu University of Science and Technology DLDarrin A. LindhoutIntarcia Therapeutics (United States)

Discussion

Member takes

Implication

May alter myofilament Ca2+ sensitivity in FHC; extends structural troponin data but leaves clinical translation open.

Structured PICO

Population

Human cardiac troponin I (cTnI) segments (cRp, cIp, cSp) and troponin C (cTnC)

Intervention

Phosphorylation (PKC sites S41, S43, T142; PAK site S149) and familial hypertrophic cardiomyopathy (FHC) mutations (R144G, R161W)

Comparator

Native (unphosphorylated, unmutated) state

Outcome

Binding affinity between cTnI segments and cTnC measured by 2D NMR spectroscopysurrogate

Phosphorylation and FHC mutations in the key functional cIp-cSp region of cardiac troponin I significantly destabilize its interaction with troponin C, which may correlate with altered myofilament function in pathophysiological conditions.

Cite This Study

Li et al. (2003) studied this question.

synapsesocial.com/papers/6a1ed460ce3e167bb87e8203 https://doi.org/10.1021/bi035408y

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Phosphorylation and Mutation of Human Cardiac Troponin I Deferentially Destabilize the Interaction of the Functional Regions of Troponin I with Troponin C,

Discussion

Member takes

Implication

Structured PICO

Cite This Study

Phosphorylation and Mutation of Human Cardiac Troponin I Deferentially Destabilize the Interaction of the Functional Regions of Troponin I with Troponin C,

Discussion

Member takes

Implication

Structured PICO

Cite This Study

Also Consider

Also Consider