Myosin assembly of smooth muscle: from ribbons and side polarity to a row polar helical model

Abstract

After decades of debate over the structure of smooth muscle myosin filaments, it is still unclear whether they are helical, as in all other muscle types, or square in shape. In both cases bipolar building units are proposed, but the deduced cross-bridge arrangements are fundamentally different. The opposite polarity of the adjusting longitudinal rows is proposed for the helical structure, while in the case of square filaments, or myosin ribbons, only their two faces are appositively polarized. Analysis of our unpublished archival data on light meromyosin (LMM) paracrystals and myosin rod assemblies as well as the filaments themselves indicated that the rods were assembled with a 6°–7° tilt angle from the rods’ longitudinal axis, in contrast to the lack of tilt in LMM, both exhibiting a 14.3 nm myosin periodicity. Optical diffraction analysis of EM images of the rod assemblies and those of intact myosin confirmed their helical architecture characterized by 28 nm residue translations, 172 nm repeats and 516 nm pitch. A detailed helical model of these filaments was elucidated with bipolar tetramer building units made of two polar trimers. The filaments elongate at their two ends in a head-to-head manner, enabling targeted cross-bridge polarity of the adjacent rows, in the form of a unique Boerdijk–Coxeter type helix, similar to that of collagen or desmin fibers, with the covalent links replaced by a head-to-head clasp.

Smooth Muscle Myosin 2 Filaments Dynamically Assemble and Stabilize During Induced Contractility

“…Further complexity could also arise from heterogenous myosin 2 subcellular functions within SMCs, as recent evidence demonstrated unique subcellular localization for SM2 and NM2 in freshly isolated primary cells (35). Finally, while the structure of NM2 bipolar filaments in cells is relatively well-established, the precise structural features of SM2 filaments in intact cells and tissues remains an active area of debate (36). Future studies to dissect unique and common biophysical properties of SM2 and NM2 filaments in SMCs should prove insightful.…”

Purification of Myosin from Bovine Tracheal Smooth Muscle, Filament Formation and Endogenous Association of Its Regulatory Complex

“…It was originally shown that the solubilized smooth muscle myosin molecule may adopt one of two possible configurations: the folded one (a loop) being more soluble, or the extended (straight) one, less soluble, aggregating to dimers and tetramers [15,16]. Such tetramers are associated with coiled-coil rods, forming what is considered in vivo the myosin filament-building units [17].…”