Coiled coil design stability

Scheme 2 shows a cross-sectional representation of a two-stranded a-helical coiled coil of 35 residues per polypeptide chain. The design of this idealized coiled coil incorporated the factors that maximize coiled-coil stability, for example, the hydrophobicity and packing effects in the hydrophobic core, intrachain electrostatic attractions, helical propensity contribution s[2324 from residues outside of the hydrophobic interface, and interchain electrostatic interactions.125 ... 

Interestingly, one can use a Cys-Gly-Gly linker at the N- or C-terminal of the polypeptide chain in the design of disulfide-bridged coiled coils. The advantage of this approach is that the Cys-Gly-Gly linker allows complete flexibility of the polypeptide chains to adopt their most stable conformation, which includes different oligomerization states, while maintaining the polypeptide chains in a parallel manner. 49 In addition, the Cys-Gly-Gly linker eliminates the monomer-dimer equilibrium and the peptide concentration effect on stability, which is observed in two-stranded coiled-coil formation of noncovalent linked polypeptides. 49 861... 

The heterostranded coiled coil shown in Figure 4 and similar molecules were designed to examine the role of interchain hydrophobic interactions in controlling the formation and stabilization of coiled coils. The question addressed was whether two Leu-Ala interactions provided more stability to the coiled coil as a heterostranded molecule than the two homostranded coiled coils which differ by having a Leu-Leu and Ala-Ala interaction. These homo- and heterostranded coiled coils have the identical amino acid composition overall and in the hydrophobic core that stabilizes the coiled-coil structure. The only difference is in the sequence of the core residues. 

Tripet, B., Wagschal, K., Lavigne, P., Mant, C. T., and Hodges, R. S. (2000). Effects of side-chain characteristics on stability and oligomerization state of a de novo-designed model coiled-coil 20 amino acid substitutions in position d. J. Mol. Biol. 300, 377-402. 

Related to these ideas, Pandya et al. (2004) have described the design of an antiparallel coiled-coil (helix-loop-helix) peptide, which is stabilized by a disulfide bridge between the termini of the peptide. Reduction of the disulfide triggered a switch to a dimeric leucine zipper. 

Based on very similar principles, though more recently, Suzuki and Fujii (1999) designed a helix-loop-helix peptide. On a related theme, the aforementioned design from Pandya et al. (2004) for a helix-loop-helix peptide stabilized by a disulfide bridge used similar ideas, although the final sequence was very different from the Myszka and Chaiken and the Suzuki and Fujii peptides, as it was also made compatible with a parallel coiled-coil dimer to promote conformational switching. 

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