Visualization of an unstable coiled coil from the scallop myosin rod

alpha-Helical coiled coils in muscle exemplify simplicity and economy of protein design: small variations in sequence lead to remarkable diversity in cellular functions(1,2). Myosin II is the key protein in muscle contraction, and the molecule's two-chain alpha-helical coiled-coil rod region-towards the carboxy terminus of the heavy chain-has unusual structural and dynamic features. The amino-terminal subfragment-2 (S2) domains of the rods can swing out from the thick filament backbone at a hinge in the coiled coil, allowing the two myosin 'heads' and their motor domains to interact with actin and generate tension(3). Most of the S2 rod appears to be a flexible coiled coil, but studies suggest that the structure at the N-terminal region is unstable(4-6), and unwinding or bending of the alpha-helices near the head-rod junction seems necessary for many of myosin's functional properties(7,8). Here we show the physical basis of a particularly weak coiled-coil segment by determining the 2.5-Angstrom-resolution crystal structure of a leucine-zipper-stabilized fragment of the scallop striated-muscle myosin rod adjacent to the head-rod junction. The N-terminal 14 residues are poorly ordered; the rest of the S2 segment forms a flexible coiled coil with poorly packed core residues. The unusual absence of inter-helical salt bridges here exposes apolar core atoms to solvent.