Visualization of an unstable coiled coil from the scallop myosin rod

• Published in: Nature (London) Vol. 424; no. 6946; pp. 341 - 345
• Main Authors: Cohen, Carolyn, Li, Yu, Brown, Jerry H, Reshetnikova, Ludmilla, Blazsek, Antal, Farkas, László, Nyitray, László
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 17.07.2003; Nature Publishing Group
• Subjects: Amino Acid Sequence; Animals; Biological and medical sciences; Crystallography, X-Ray; Fundamental and applied biological sciences. Psychology; Hydrophobic and Hydrophilic Interactions; Marine; Models, Molecular; Molecular and cellular biology; Molecular Sequence Data; Mollusca - chemistry; Myosin Type II - chemistry; Pectinidae; Pliability; Protein Structure, Secondary; Protein Structure, Tertiary; Proteins; Solvents - chemistry; Static Electricity; Visualization; Genetics
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature01801

α-Helical coiled coils in muscle exemplify simplicity and economy of protein design: small variations in sequence lead to remarkable diversity in cellular functions. Myosin II is the key protein in muscle contraction, and the molecule's two-chain α-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. 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, and unwinding or bending of the α-helices near the head-rod junction seems necessary for many of myosin's functional properties. Here we show the physical basis of a particularly weak coiled-coil segment by determining the 2.5- -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 interhelical salt bridges here exposes apolar core atoms to solvent.