AI Article Synopsis
- The study investigated four mutations in troponin I linked to cardiomyopathy, focusing on how these mutations affect the function of thin filaments.
- The R193H mutant showed increased ATPase activity regardless of calcium presence, suggesting it stabilizes the active state of thin filaments, while the other mutations (D191H, R146G, R146W) exhibited varying ATPase activity depending on calcium levels.
- Overall, the findings indicate that changes in the normal actomyosin state distribution can lead to cardiomyopathy, highlighting the specific role of the intermediate state in enhancing myosin's ATP hydrolysis rate.
Article Abstract
We examined four cardiomyopathy-causing mutations of troponin I that appear to disturb function by altering the distribution of thin filament states. The R193H (mouse) troponin I mutant had greater than normal actin-activated myosin-S1 ATPase activity in both the presence and absence of calcium. The rate of ATPase activity was the same as that of the wild-type at near-saturating concentrations of the activator, N-ethylmaleimide-S1. This mutant appeared to function by stabilizing the active state of thin filaments. Mutations D191H, R146G, and R146W had lower ATPase activities in the presence of calcium, but higher activities in the absence of calcium. These effects were most pronounced with mutations at position 146. For all three mutants the rates were similar to those of the wild-type at near-saturating concentrations of N-ethylmaleimide-S1. These results, combined with previous results, show that any alteration in the normal distribution of actomyosin states is capable of producing cardiomyopathy. The results of the D191H, R146G, and R146W mutations are most readily explained if the intermediate state of regulated actin has a unique function. The intermediate state appears to have an ability to accelerate the rate of ATP hydrolysis by myosin that exceeds that of the inactive state.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2717271 | PMC |
| http://dx.doi.org/10.1016/j.bpj.2008.12.3909 | DOI Listing |
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