دورية أكاديمية
Functional significance of HCM mutants of tropomyosin, V95A and D175N, studied with in vitro motility assays
| العنوان: | Functional significance of HCM mutants of tropomyosin, V95A and D175N, studied with in vitro motility assays |
|---|---|
| المؤلفون: | Shuya Ishii, Madoka Suzuki, Shin’ichi Ishiwata, Masataka Kawai |
| المصدر: | Biophysics and Physicobiology, Vol 16 (2019) |
| بيانات النشر: | The Biophysical Society of Japan, 2019. |
| سنة النشر: | 2019 |
| المجموعة: | LCC:Biology (General) LCC:Physiology LCC:Physics |
| مصطلحات موضوعية: | hypertrophic cardiomyopathy, tropomyosin mutants, tirf, optical tweezers, sliding velocity and force, Biology (General), QH301-705.5, Physiology, QP1-981, Physics, QC1-999 |
| الوصف: | The majority of hypertrophic cardiomyopathy (HCM) is caused by mutations in sarcomere proteins. We examined tropomyosin (Tpm)’s HCM mutants in humans, V95A and D175N, with in vitro motility assay using optical tweezers to evaluate the effects of the Tpm mutations on the actomyosin interaction at the single molecular level. Thin filaments were reconstituted using these Tpm mutants, and their sliding velocity and force were measured at varying Ca2+ concentrations. Our results indicate that the sliding velocity at pCa ≥8.0 was significantly increased in mutants, which is expected to cause a diastolic problem. The velocity that can be activated by Ca2+ decreased significantly in mutants causing a systolic problem. With sliding force, Ca2+ activatable force decreased in V95A and increased in D175N, which may cause a systolic problem. Our results further demonstrate that the duty ratio determined at the steady state of force generation in saturating [Ca2+] decreased in V95A and increased in D175N. The Ca2+ sensitivity and cooperativity were not significantly affected by the mutations. These results suggest that the two mutants modulate molecular processes of the actomyosin interaction differently, but to result in the same pathology known as HCM. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2189-4779 |
| Relation: | https://doaj.org/toc/2189-4779 |
| DOI: | 10.2142/biophysico.16.0_28 |
| URL الوصول: | https://doaj.org/article/423670eecd3d423badd94114977a97eb |
| رقم الأكسشن: | edsdoj.423670eecd3d423badd94114977a97eb |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 21894779 |
|---|---|
| DOI: | 10.2142/biophysico.16.0_28 |