a-Helix-to-Random Coil Transitions of Two-Chain, Coiled Coils. Application to a Synthetic Analogue of Tropomyosin

A theory developed previously for the stability of the native structure in two-chain, a-helical coiled coils is applied to singly (disulfide) cross-linked tropomyosin and to a singly (disulfide) cross-linked, synthetic, 43-residue peptide analogue (called here XY5) of tropomyosin. Algorithms are obtained from fits of extant data for the helix stability parameter (s) for each amino acid residue type as a function of temperature; these reproduce the data to high precision. Extant data for the helix initiation parameter (a) are used as is. Employing these s and u values to realize the theory and using extant thermal denaturation data for XY5 and for tropomyosin, we have determined the temperature dependence of the helix-helix interaction parameter w(T) of the theory for the two substances. These w(T) functions then allow smoothed theoretical fits of thermal denaturation data and calculation of helix probability profiles along the polypeptide chains for XY5 and for tropomyosin. Theoretical predictions are generated concerning the thermal denaturation and helix probability profiles of yet unsynthesized, longer chain homologues (XY,) of the synthetic material XY5, including XY39, whose 281-residue chain would more closely model the 284-residue chain of tropomyosin. The importance of degree of polymerization in dictating helix content and profile and the difficulties in choosing models to match both the u and s(T) values that govern short-range interactions and the u(T) that governs interhelix interactions are clearly demonstrated. Thermodynamic implications of the w(T) functions obtained are discussed and shown to imply algebraic signs for standard enthalpy, entropy, and heat capacity changes that are difficult to reconcile with the expected hydrophobic and salt-bridge nature of the interactions. Predictions are generated concerning the behavior of non-cross-linked XY5, for which very few data are available. Some possible future directions of theory and experiment are outlined.