Ca2+-induced conformational transition in the inhibitory and regulatory regions of cardiac troponin I

Wen-Ji Dong; John M Robinson; Scott Stagg; Jun Xing; Herbert C Cheung

doi:10.1074/jbc.M212886200

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Ca2+-induced conformational transition in the inhibitory and regulatory regions of cardiac troponin I

Journal article

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Peer reviewed

Ca2+-induced conformational transition in the inhibitory and regulatory regions of cardiac troponin I

Wen-Ji Dong, John M Robinson, Scott Stagg, Jun Xing and Herbert C Cheung

The Journal of biological chemistry, Vol.278(10), pp.8686-8692

03/07/2003

DOI: https://doi.org/10.1074/jbc.M212886200

Handle:

https://hdl.handle.net/2376/103523

PMID: 12511564

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Abstract

Recombinant Proteins - metabolism

Amino Acid Sequence

Calcium - metabolism

Models, Molecular

Molecular Sequence Data

Recombinant Proteins - chemistry

Spectrometry, Fluorescence

Animals

Chickens

Myocardium - metabolism

Protein Conformation

Energy Transfer

Troponin I - chemistry

Troponin I - metabolism

Naphthalenesulfonates

Cardiac muscle activation is initiated by the binding of Ca(2+) to the single N-domain regulatory site of cardiac muscle troponin C (cTnC). Ca(2+) binding causes structural changes between cTnC and two critical regions of cardiac muscle troponin I (cTnI): the regulatory region (cTnI-R, residues 150-165) and the inhibitory region (cTnI-I, residues130-149). These changes are associated with a decreased cTnI affinity for actin and a heightened affinity for cTnC. Using Förster resonance energy transfer, we have measured three intra-cTnI distances in the deactivated (Mg(2+)-saturated) and Ca(2+)-activated (Ca(2+)-saturated) states in reconstituted binary (cTnC-cTnI) and ternary (cTnC-cTnI-cTnT) troponin complexes. Distance A (spanning cTnI-R) was unaltered by Ca(2+). Distances B (spanning both cTnI-R and cTnI-I) and C (from a residue flanking cTnI-I to a residue in the center of cTnI-R) exhibited Ca(2+)-induced increases of >8 A. These results compliment our previous determination of the distance between residues flanking cTnI-I alone. Together, the data suggest that Ca(2+) activation causes residues within cTnI-I to switch from a beta-turn/coil to an extended quasi-alpha-helical conformation as the actin-contacts are broken, whereas cTnI-R remains alpha-helical in both Mg(2+)- and Ca(2+)-saturated states. We have used the data to construct a structural model of the cTnI inhibitory and regulatory regions in the Mg(2+)- and Ca(2+)-saturated states.

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Title: Ca2+-induced conformational transition in the inhibitory and regulatory regions of cardiac troponin I
Creators: Wen-Ji Dong - Department of Biochemistry and Molecular Genetics, University of Alabama, Birmingham 35294-2041, USA
John M Robinson
Scott Stagg
Jun Xing
Herbert C Cheung
Publication Details: The Journal of biological chemistry, Vol.278(10), pp.8686-8692
Academic Unit: Chemical Engineering and Bioengineering, School of
Publisher: United States
Grant note: HL52508 / NHLBI NIH HHS
Identifiers: 99900546672001842
Language: English
Resource Type: Journal article