The troponin I inhibitory peptide (96-115) maintains a predominantly extended conformation, possibly kinked at Gly104, both free and when bound to troponin C, which may facilitate its alternating binding to actin or TnC during the contractile cycle.
May refine thin filament regulation models; leaves open relevance to human cardiac therapies.
We have utilized CD and NMR spectroscopy to study the conformation of the troponin I (TnI) inhibitory peptide [TnI(96-115)] free in solution and when bound to troponin C (TnC). Analysis of the CD spectrum of the free peptide in aqueous solution indicates it is only approximately 3% helix. Upon complex formation with TnC, there is no change in total helix content compared to the sum of the free components. The NMR data support a predominantly extended conformation for the free peptide. TnI(96-115) bound to TnC was selectively observed by NMR using deuterated TnC (dTnC). For the 1:1 ratio of TnI(96-115) to dTnC used, 95% of the peptide was bound to dTnC. The chemical shifts of the TnC-bound peptide resonances are similar to those of the free peptide, indicating that the change in peptide conformation as a consequence of binding to TnC is small. For the TnC-bound TnI(96-115) peptide, the ratios of sequential Halpha-HN to intraresidue HN-Halpha NOE cross-peak volumes support a predominantly extended conformation, possibly kinked at Gly104. The results presented here are in agreement with sequence analysis predictions for TnI(96-115) as a free peptide or within the intact TnI sequence. The predominantly extended structure for the 96-115 inhibitory sequence segment of TnI with a kink at Gly104 may facilitate its binding alternately to actin or TnC in response to the Ca2+ signals that control thick and thin filament interactions during the contractile cycle.
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Hernández et al. (1999) studied this question.
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