RT Journal Article
SR Electronic
T1 Single molecule analysis reveals the role of regulatory light chains in fine-tuning skeletal myosin-II function
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.01.21.913558
DO 10.1101/2020.01.21.913558
A1 Arnab Nayak
A1 Tianbang Wang
A1 Peter Franz
A1 Walter Steffen
A1 Igor Chizhov
A1 Georgios Tsiavaliaris
A1 Mamta Amrute-Nayak
YR 2020
UL http://biorxiv.org/content/early/2020/01/21/2020.01.21.913558.abstract
AB Myosin II is the main force generating motor during muscle contraction. Myosin II exists as different isoforms, involved in diverse physiological functions. The outstanding question is whether the myosin heavy chain (MHC) isoforms alone account for the distinct physiological properties. Unique sets of essential and regulatory light chains (RLCs) assembled with specific MHCs raises an interesting possibility of specialization of myosin functions via light chains (LCs). Here, we ask whether different RLCs contribute to the functional diversification. To investigate this, we generated chimeric motors by reconstituting MHC fast isoform (MyHC-IId) and slow isoform (MHC-I) with different light chain variants. As a result of RLCs swapping, actin filament sliding velocity increased by ∼ 10 fold for the slow myosin and decreased by >3 fold for the fast myosin. Ensemble molecule solution kinetics and single molecule optical trapping measurements provided in-depth insights into altered chemo mechanical properties of the myosin motors, thereby affecting the sliding speed. We find that both slow and fast myosins mechanical output is sensitive to the RLC isoform and propose that RLCs are crucial in fine-tuning of the myosin function.