Solvent-induced distortions and the curvature of α-helices

Abstract

The alpha-helix defined in 1951 by Pauling et al. on the basis of model building and X-ray fibre diffraction data has 3.65 residues per turn (n) achieved with planar peptides, torsion angles of phi = -48 degrees and psi = -57 degrees and hydrogen bonds which are close to linear. Although X-ray analyses of proteins have confirmed the general correctness of the model for the helix, recent high resolution (1.7-1.0 A) diffraction studies have shown that the parameters described by Pauling et al. and later by Perutz and Arnott and Wonacott are not a good description of the alpha-helices in globular proteins, where the mean values of phi, psi are usually close to -63 degrees, -42 degrees. Here we show that these values arise as a mean of two significantly different classes in amphipathic helices depending on whether the peptide carbonyl oxygen is hydrogen bonded to a solvent or polar side-chain atom. The hydrogen bonds made by the hydrophilic carbonyls to the NH groups within helices are longer and less linear than those involving hydrophobic carbonyls. We also show that these effects are associated with a significant curvature of helices in globular proteins. For example, the alpha-helix in avian pancreatic peptide (aPP) has a radius of curvature of approximately 70 A. These results are of significance in the packing of helices in fibrous and globular proteins, in the calculation of their dipole moments, solvent accessibilities and internal energies, and in the theoretical estimation of spectroscopic properties such as circular dichroism and Raman scattering.

Multiple alanine replacements within α‐helix 126–134 of T4 lysozyme have independent, additive effects on both structure and stability

“…For Asp 127, Glu 128, and Val 131 the average of the pseudo torsion angles formed by the a-carbon, carbonyl carbon, carbonyl oxygen, and water molecule is 22 f 3". All of these values are very close to those normally observed for water molecules bound to the solvent-exposed residues in the center of an amphiphilic a-helix (Blundell et al, 1983;Baker & Hubbard, 1984;Barlow & Thornton, 1988). Because Ala 130 is partially buried it prevents the bound solvent (#216) at this position from having the standard 22" angle.…”

“…The idea of the latter comparison was that it would help allow for a situation in which the overall helix was slightly bent. In particular, it is known (Blundell et al, 1983) that buried hydrogen bonds tend to be shorter than those exposed to solvent, and this is true for a-helix 126-134 of T4 lysozyme (Table 8). The comparisons shown in Table 9 tend to support the general trend discussed above, namely that the Leu 133 -+ Ala replacement makes the helix less regular, and that multiple alanine replacements restore regularity.…”

The influence of proline residues on α‐helical structure

“…Thus, surface helices always kink around the core of a protein, i.e. a proline residue within a helix appears to be used to accentuate the curvature often observed in helices lying on the surface of a protein [17,18]. Proline kinking of long helices may have this additional function to ensure good packing of the structures with the protein.…”

Secondary structure and dosage of soluble and membrane proteins by attenuated total reflection Fourier‐transform infrared spectroscopy on hydrated films

“…Any distortion of the a-helix would also shift the frequency of the amide-I-associated band. Such distorsions have been recently described in protein crystals [42]. It therefore appears wiser to consider the individual components determined by the curve fitting as a mixture of many subcomponents with slightly different frequencies.…”