Tropomyosin movement on F-actin during muscle activation explained by energy landscapes
Muscle contraction is regulated by tropomyosin movement across the thin filament surface, which exposes or blocks myosin-binding sites on actin. Recent atomic structures of F-actin-tropomyosin have yielded the positions of tropomyosin on myosin-free and myosin-decorated actin. Here, the repositionin...
Gespeichert in:
| Hauptverfasser: | , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
8 January 2014
|
| In: |
Archives of biochemistry and biophysics
Year: 2014, Jahrgang: 545, Pages: 63-68 |
| ISSN: | 1096-0384 |
| DOI: | 10.1016/j.abb.2014.01.001 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.abb.2014.01.001 Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S0003986114000046 
|
| Verfasserangaben: | Marek Orzechowski, Jeffrey R. Moore, Stefan Fischer, William Lehman |
| Zusammenfassung: | Muscle contraction is regulated by tropomyosin movement across the thin filament surface, which exposes or blocks myosin-binding sites on actin. Recent atomic structures of F-actin-tropomyosin have yielded the positions of tropomyosin on myosin-free and myosin-decorated actin. Here, the repositioning of α-tropomyosin between these locations on F-actin was systematically examined by optimizing the energy of the complex for a wide range of tropomyosin positions on F-actin. The resulting energy landscape provides a full-map of the F-actin surface preferred by tropomyosin, revealing a broad energy basin associated with the tropomyosin position that blocks myosin-binding. This is consistent with previously proposed low-energy oscillations of semi-rigid tropomyosin, necessary for shifting of tropomyosin following troponin-binding. In contrast, the landscape shows much less favorable energies when tropomyosin locates near its myosin-induced “open-state” position. This indicates that spontaneous movement of tropomyosin away from its energetic “ground-state” to the open-state is unlikely in absence of myosin. Instead, myosin-binding must drive tropomyosin toward the open-state to activate the thin filament. Additional energy landscapes were computed for disease-causing actin mutants that distort the topology of the actin-tropomyosin energy landscape, explaining their phenotypes. Thus, the computation of such energy landscapes offers a sensitive way to estimate the impact of mutations. |
|---|---|
| Beschreibung: | Gesehen am 21.09.2020 |
| Beschreibung: | Online Resource |
| ISSN: | 1096-0384 |
| DOI: | 10.1016/j.abb.2014.01.001 |