The effect of conformation on the CD of interacting helices: a theoretical study of tropomyosin.

A recent report [M. E. Holtzer, et al. (1988) Biophysics Journal, 53, 96a] of the anomalous CD spectrum of the tropomyosin (TM) fragment 11TM127 motivated us to model the system as two 21-residue alpha-helices distorted to a coiled-coil conformation. We used strong-coupling exciton theory to model the optical properties of the system. Two backbone amide excited states (n pi* and pi pi*) were considered, as well as four excited states (Lb, La, Bb, Ba) for the phenolic side chain. We calculated the effect of superhelix formation on the backbone CD spectrum. The decrease in molar ellipticity of the alpha-helix parallel-polarized transition at 208 nm was found to be a simple function of superhelix tilt angle. We then modeled a coiled coil (radius = 5.5 A, pitch = -140 A) with one aromatic ring per superhelix. Steric interactions between aromatic side chains in a coiled coil were calculated as a function of side-chain conformation and heptet position. Steric interactions between phenolic rings will be significant for heptet positions a and d, but not for positions b, c, e, f, or g. We calculated the phenolic Lb transition rotational strength as a function of position within the heptet repeats, and of all possible side-chain dihedral angles, chi 1 and chi 2. When tyrosines were placed at heptet positions b, c, e, f, or g, the rotational-strength surface was nearly identical to that of a single tyrosine in an undistorted helix. In contrast, the rotational-strength surface for tyrosines in heptet positions a or d showed substantial intertyrosine coupling components. The rotational-strength surfaces for the three types of heptet positions (position a, position d, and the others) allowed an interpretation of the aromatic CD spectra of TM and its fragments. It was predicted that the three types of heptet positions will be spectroscopically distinguishable.