Structural model of weak-binding actomyosin in the prepowerstroke state [Protein Structure and Folding]

November 21st, 2014 by Varkuti, B. H., Yang, Z., Malnasi-Csizmadia, A.

We present the first in silico model of the weak−binding actomyosin in the initial powerstroke state, representing the actin-binding induced major structural changes in myosin. First, we docked an actin trimer to prepowerstroke myosin then relaxed the complex by a 100−ns−long unrestrained molecular dynamics. In the first few nanoseconds , actin-binding induced an extra primed myosin state i.e. the further priming of the myosin lever by 18 degrees coupled to a further closure of switch 2 loop. We demonstrated that actin induces the extra primed state of myosin specifically through the actin N−terminus−activation loop interaction. The applied in silico methodology was validated by forming rigor structures which perfectly fitted into an experimentally determined EM map of the rigor actomyosin. Our results unveiled the role of actin in the powerstroke by presenting that actin moves the myosin lever to the extra primed state which leads to the effective lever swing.