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

Nicole M. Cordina, Chu Kong Liew, David A. Gell, Piotr G. Fajer, Joel P. Mackay, Louise J. Brown*

*Corresponding author for this work

Research output: Contribution to journalArticle

12 Citations (Scopus)

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. Published by Wiley-Blackwell.

Original languageEnglish
Pages (from-to)1376-1387
Number of pages12
JournalProtein science : a publication of the Protein Society
Volume21
Issue number9
DOIs
Publication statusPublished - Sep 2012

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