title: Considerations in the design and optimization of coiled coil structures.
abstract: Coiled coil motifs are, despite their apparent simplicity, highly specific, and play a significant role in the understanding of tertiary structure and its formation. The most commonly observed of the coiled coils, the parallel dimeric, is yet to be fully characterized for this structural class in general. Nonetheless, strict rules have emerged for the necessity of specific types of amino acids at specific positions. In this chapter, we discuss this system in light of existing coiled coil structures and in applying rules to coiled coils that are to be designed or optimized. Understanding and expanding on these rules is crucial in using these motifs, which play key roles in virtually every cellular process, to act as drug-delivery agents by sequestering other proteins that are not behaving natively or that have been upregulated (for example, by binding to coiled coil domains implicated in oncogenesis). The roles of the a and d "hydrophobic" core positions and the e and g "electrostatic" edge positions in directing oligomerization and pairing specificity are discussed. Also discussed is the role of these positions in concert with the b, c, and f positions in maintaining alpha-helical propensity, helix solubility, and dimer stability.
authors.affiliation: Institut für Biologie III, Universität Freiburg, Germany.
authors.forename: Jody M
authors.initials: JM
authors.lastname: Mason
authors.forename: Kristian M
authors.initials: KM
authors.lastname: Müller
authors.forename: Katja M
authors.initials: KM
authors.lastname: Arndt
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019295:Computational Biology; D019281:Dimerization; D019077:Helix-Turn-Helix Motifs; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015202:Protein Engineering; D017510:Protein Folding; D012995:Solubility