The myosin II coiled-coil domain atomic structure in its native environment

Abstract

The atomic structure of the complete myosin tail within thick filaments isolated from Lethocerus indicus flight muscle is described and compared to crystal structures of recombinant, human cardiac myosin tail segments. Overall, the agreement is good with three exceptions: the proximal S2, in which the filament has heads attached but the crystal structure doesn’t, and skip regions 2 and 4. At the head–tail junction, the tail α-helices are asymmetrically structured encompassing well-defined unfolding of 12 residues for one myosin tail, ∼4 residues of the other, and different degrees of α-helix unwinding for both tail α-helices, thereby providing an atomic resolution description of coiled-coil “uncoiling” at the head–tail junction. Asymmetry is observed in the nonhelical C termini; one C-terminal segment is intercalated between ribbons of myosin tails, the other apparently terminating at Skip 4 of another myosin tail. Between skip residues, crystal and filament structures agree well. Skips 1 and 3 also agree well and show the expected α-helix unwinding and coiled-coil untwisting in response to skip residue insertion. Skips 2 and 4 are different. Skip 2 is accommodated in an unusual manner through an increase in α-helix radius and corresponding reduction in rise/residue. Skip 4 remains helical in one chain, with the other chain unfolded, apparently influenced by the acidic myosin C terminus. The atomic model may shed some light on thick filament mechanosensing and is a step in understanding the complex roles that thick filaments of all species undergo during muscle contraction.

Structure of the Flight Muscle Thick Filament from the Bumble Bee, Bombus ignitus, at 6 Å Resolution

“…It is tilted slightly toward the bare zone. The position is essentially identical to that found in [21], except for Skip 1 where the Lethocerus atomic model falls outside the Bombus envelope due to the latter's different azimuthal rotation when compared with Lethocerus (white). (B) Superposition of curved layers from Lethocerus (white) and Bombus (blue).…”

“…Without Skip 3, the WRY domain cannot nestle between the rods, but the extended polypeptide chain of flightin still can pass through the curved layers at both ends. Skip angled significantly with respect to the filament axis [21]. The Skip 1 accommodation region in Bombus is significantly less angled relative to the filament axis than in Lethocerus.…”

“…We used rigid-body fitting in Chimera [20] to compare the four Bombus myosin tail segments containing skip residues with the corresponding segments in the atomic model of the Lethocerus flight muscle myosin tail [21] (Figure 2A). Skips 2 and 3 of both atomic models aligned well.…”

“…The most significant difference is seen in Skip 1. The accommodation region of Skip 1, which is where the coiled-coil changes structure to parallel α-helices in order to accommodate the inserted amino acid residue, in Lethocerus consists of ~30 residues of parallel α-helices angled significantly with respect to the filament axis [21]. The Skip 1…”

Validate the force-velocity relation of the Hill’s muscle model from a molecular perspective

“…Frontiers in Bioengineering and Biotechnology frontiersin.org 2010; Yang et al, 2020;Rahmani et al, 2021). Based on these investigations, myosin-II can be mainly classified into three domains: the head domain, the lever arm domain, and the tail domain.…”