The role of the skeletal muscle myosin light chains N‐terminal fragments

Abstract

The myosin regulatory and essential fight chains in skeletal muscle do not play a role as significant as in scallop or smooth muscle, however, there are some data suggesting that the skeletal myosin fight chains and their N-terminal parts may have a modulatory function in the interaction of actin with myosin heads. In this paper four conformational states of the myosin head with respect to the regulatory light chain bound cation (magnesium or calcium) and phosphorylation are proposed. Communication between regulatory and essential light chains and putative binding of the N-terminus of A1 essential light chain to actin is discussed.

Different actin affinities of human cardiac essential myosin light chain isoforms

“…We could demonstrate that G‐actin binds to affinity beads. This shows for the first time that the N‐terminal sequence 4–14 of human cardiac VLC‐1 indeed interacts with actin as recently demonstrated for skeletal muscle MLC‐1 [11–13]. Pre‐incubation of G‐actin with the N‐terminal peptide 5–14 of VLC‐1 prevented actin from binding to the affinity beads at a peptide concentration of around 1 μM.…”

“…The molecular mechanism explaining the effects of essential MLC on the cross‐bridges in the heart may reside in the mode of interaction between MLC‐1 and actin. It has been demonstrated that the amino‐terminal domain of MLC‐1 isoforms interact with the carboxyl‐terminal domain of actin [11–13]. This interaction could be of functional importance since inhibition of this interaction using synthetic peptides increased force production and shortening velocity of human heart fibers [14]and myofibrillar ATPase [15].…”

Molecular modeling of the myosin-S1(A1) isoform

“…This could explain the Ca 2+ dependency of A1 binding to regulated actin (Trayer and Trayer, 1985), since Ca 2+ binding to troponin C reduced actin affinity of troponin I (Rü egg, 1986) and may, therefore loose its inhibitory effect on A1 binding to actin during muscle activation. Furthermore, in the presence of Ca 2+ , a more extended conformation of the N-terminus of A1 occurs, making this domain more susceptible to papain cleavage (Stepkowski, 1995), and a much tighter binding to actin could be observed (Nieznanski et al, 2003).…”

Minigenes encoding N‐terminal domains of human cardiac myosin light chain‐1 improve heart function of transgenic rats

“…This could explain the Ca 2ϩ dependency of MLC-1 binding to regulated actin (19), since Ca 2ϩ binding to troponin C reduced actin affinity of troponin I (28) and therefore may lose its inhibitory effect on MLC-1 binding to actin during muscle activation. Furthermore, in the presence of Ca 2ϩ , a more extended conformation of the NH 2 terminus of MLC-1 occurs, making this domain more susceptible to papain cleavage (29), and a much tighter binding to actin could be observed (30).…”