What is the clinical evidence from this study?

Study design: Other. Intervention: Bisphosphorylation of cardiac TnI vs. Unphosphorylated TnI. Primary outcome: Interaction between TnI and TnC.

What question did this study set out to answer?

To elucidate how protein kinase A-mediated bisphosphorylation of the cardiac troponin I N-terminal extension disrupts interactions with troponin C to accelerate calcium release.

March 6, 2004Biochemistry

Characterization of the Interaction between the N-Terminal Extension of Human Cardiac Troponin I and Troponin C

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Key result

Bisphosphorylation of cardiac troponin I weakens the interaction between the region immediately C-terminal to the phosphorylation sites and troponin C.

Population

Human cardiac troponin I (TnI) N-terminal fragments (residues 1-18, 1-29, and 1-64) and troponin C (TnC)

Comparison

Bisphosphorylation of the N-terminal extension… vs Unphosphorylated TnI fragments

Design

Preclinical

Authors

DWDouglas G. WardCancer Research UK Clinical Trials Unit SBSusan BrewerStanford University MCMelanie CalvertHeart Failure & Transplant

Discussion

Member takes

Implication

Extends troponin I-C interaction models; leaves open translation to human cardiac physiology.

Key Points

To elucidate how protein kinase A-mediated bisphosphorylation of the cardiac troponin I N-terminal extension disrupts interactions with troponin C to accelerate calcium release.
Analyzed binding interactions between intact troponin C and human cardiac troponin I fragments (residues 1-18, 1-29, and 1-64) in unphosphorylated and bisphosphorylated states using proton nuclear magnetic resonance spectroscopy.
Assessed potential secondary structural alterations induced by bisphosphorylation in troponin I fragment 1-64 using circular dichroism spectroscopy.
Troponin I fragment 1-18 showed no binding to troponin C, whereas unphosphorylated fragment 1-29 bound via its C-terminal region; bisphosphorylation strongly weakened this interaction.
Troponin C binding broadened nuclear magnetic resonance signals from residues immediately C-terminal to the phosphorylation sites in fragment 1-64, an effect attenuated by bisphosphorylation without producing major secondary structure changes.

Structured PICO

Population

Human cardiac troponin I (TnI) N-terminal fragments (residues 1-18, 1-29, and 1-64) and troponin C (TnC)

Intervention

Bisphosphorylation of the N-terminal extension of TnI

Comparator

Unphosphorylated TnI fragments

Outcome

Interaction between TnI fragments and TnC, assessed via (1)H NMR and circular dichroismsurrogate

Bisphosphorylation of cardiac troponin I weakens its interaction with troponin C, elucidating the molecular mechanism of accelerated calcium release following beta-adrenergic stimulation.

Cite This Study

Ward et al. (2004) studied this question. Bisphosphorylation of cardiac TnI vs. Unphosphorylated TnI was evaluated on Interaction between TnI and TnC. Bisphosphorylation of cardiac troponin I weakens the interaction between the region immediately C-terminal to the phosphorylation sites and troponin C.

synapsesocial.com/papers/6a15cc9f814bf8ec9a4f0eb0 https://doi.org/10.1021/bi036128l

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Characterization of the Interaction between the N-Terminal Extension of Human Cardiac Troponin I and Troponin C

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Characterization of the Interaction between the N-Terminal Extension of Human Cardiac Troponin I and Troponin C

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Also Consider