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Interdomain orientation of cardiac Troponin C characterized by paramagnetic relaxation enhancement NMR reveals a compact state

Citation

Cordina, NM and Liew, CK and Gell, DA and Fajer, PG and Mackay, JP and Brown, LJ, Interdomain orientation of cardiac Troponin C characterized by paramagnetic relaxation enhancement NMR reveals a compact state, Protein Science, 21, (9) pp. 1376-1387. ISSN 1469-896X (2012) [Refereed Article]

Copyright Statement

Copyright 2012 The Protein Society

DOI: doi:10.1002/pro.2124

Abstract

Cardiac troponin C (cTnC) is the calcium binding subunit of the troponin complex that triggers the thin filament response to calcium influx into the sarcomere. cTnC consists of two globular EF-hand domains (termed the N- and C-domains) connected by a flexible linker. While the conformation of each domain of cTnC has been thoroughly characterized through NMR studies involving either the isolated N-domain (N-cTnC) or C-domain (C-cTnC), little attention has been paid to the range of interdomain orientations possible in full-length cTnC that arises as a consequence of the flexibility of the domain linker. Flexibility in the domain linker of cTnC is essential for effective regulatory function of troponin. We have therefore utilized paramagnetic relaxation enhancement (PRE) NMR to assess the interdomain orientation of cTnC. Ensemble fitting of our interdomain PRE measurements reveals that isolated cTnC has considerable interdomain flexibility and preferentially adopts a bent conformation in solution, with a defined range of relative domain orientations.

Item Details

Item Type:Refereed Article
Keywords:cardiac troponin C, solution NMR, paramagnetic relaxation enhancement, site-directed spin labeling, ensemble states
Research Division:Biological Sciences
Research Group:Biochemistry and Cell Biology
Research Field:Structural Biology (incl. Macromolecular Modelling)
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cardiovascular System and Diseases
Author:Gell, DA (Dr David Gell)
ID Code:79772
Year Published:2012
Web of Science® Times Cited:9
Deposited By:Menzies Institute for Medical Research
Deposited On:2012-10-02
Last Modified:2017-11-20
Downloads:0

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