Is there nascent structure in the intrinsically disordered region of troponin I?

Olivier Julien, Pascal Mercier, Claire N. Allen, Olivier Fisette, Carlos H. I. Ramos, Patrick Lagüe, Tharin M. A. Blumenschein, Brian D. Sykes

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21 Citations (Scopus)


In striated muscle, the binding of calcium to troponin C (TnC) results in the removal of the C-terminal region of the inhibitory protein troponin I (TnI) from actin. While structural studies of the muscle system have been successful in determining the overall organization of most of the components involved in force generation at the atomic level, the structure and dynamics of the C-terminal region of TnI remains controversial. This domain of TnI is highly flexible, and it has been proposed that this intrinsically disordered region (IDR) regulates contraction via a “fly-casting” mechanism. Different structures have been presented for this region using different methodologies: a single a-helix, a “mobile domain” containing a small ß-sheet, an unstructured region, and a two helix segment. To investigate whether this IDR has in fact any nascent structure, we have constructed a skeletal TnC-TnI chimera that contains the N-domain of TnC (1–90), a short linker (GGAGG), and the C-terminal region of TnI (97–182) and have acquired 15N NMR relaxation data for this chimera. We compare the experimental relaxation parameters with those calculated from molecular dynamic simulations using four models based upon the structural studies. Our experimental results suggest that the C-terminal region of TnI does not contain any defined secondary structure, supporting the “fly-casting” mechanism. We interpret the presence of a “plateau” in the 15N NMR relaxation data as being an intrinsic property of IDRs. We also identified a more rigid adjacent region of TnI that has implications for muscle performance under ischemic conditions.
Original languageEnglish
Pages (from-to)1240-1250
Number of pages11
JournalProteins: Structure, Function, and Bioinformatics
Issue number4
Publication statusPublished - Apr 2011

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