The Myosin II Coiled-Coil Domain Atomic Structure in its Native Environment Hamidreza Rahmani, Zhongjun Hu, Nadia Daneshparvar, Dianne W. Taylor and Kenneth A. Taylor The atomic structure of the complete myosin tail of native thick filaments 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, where 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 and ~6 residues of the other. Different degrees of α-helix unwinding are observed for both α-helices, thereby providing an atomic resolution description of coiled-coil “uncoiling” at the head-tail junction. Asymmetry is observed in the non-helical 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 the 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 the phenomenon of thick filament mechanosensing and is a first step in understanding the complex roles that thick filaments of all species undergo during muscle contraction.