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Type: Artigo de periódico
Title: Is there nascent structure in the intrinsically disordered region of troponin I?
Author: Julien, O
Mercier, P
Allen, CN
Fisette, O
Ramos, CHI
Lague, P
Blumenschein, TMA
Sykes, BD
Abstract: 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 alpha-helix, a "mobile domain'' containing a small beta-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 (15)N 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 (15)N 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.
Subject: NMR
muscle regulation
protein dynamics
molecular dynamics
NMR relaxation
Country: EUA
Editor: Wiley-blackwell
Citation: Proteins-structure Function And Bioinformatics. Wiley-blackwell, v. 79, n. 4, n. 1240, n. 1250, 2011.
Rights: fechado
Identifier DOI: 10.1002/prot.22959
Date Issue: 2011
Appears in Collections:Unicamp - Artigos e Outros Documentos

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