Structural specificity in coiled-coil interactions

Abstract

Coiled coils have a rich history in the field of protein design and engineering. Novel structures, such as the first seven-helix coiled coil, continue to provide surprises and insights. Large-scale datasets quantifying the influence of systematic mutations on coiled-coil stability are a valuable new asset to the area. Scoring methods based on sequence and/or structure can predict interaction preferences in coiled-coil-mediated bZIP transcription factor dimerization. Experimental and computational methods for dealing with the near-degeneracy of many coiled-coil structures appear promising for future design applications.

Figure 1

Helical wheels for coiled coils of varying topology. Heptad positions are shown in small letters, with gray and orange circles indicating predominantly hydrophobic and predominantly polar/charged residues, respectively. A The canonical 3–4 heptad repeat, in which hydrophobic residues are 3 and 4 amino acids apart, is found for many coiled coils including dimers (shown in the figure), trimers and tetramers. Prime notation (e.g. a’) in this figure and throughout the main text is used to indicate a residue on the opposite chain. B An antiparallel tetramer with a 3-3-1 repeat, as in Figure 2B and reference [14]. C A parallel seven-helix coiled coil with a 3-1-2-1 hydrophobic pattern, as in Figure 2D and reference [19]. Note that these hydrophobic patterns do not uniquely specify these structures. Other features, including a-a’ asparagine hydrogen bonding, can be important. Helical wheels were made using DrawCoil 1.0 (http://www.gevorggrigoryan.com/drawcoil/)

Figure 2

New and interesting coiled-coil structures. Each coiled coil is shown axially and from the side. Color indicates helix orientation: blue – N-terminus, red – C-terminus. A, B and D Show variants of a GCN4-derived coiled coil with altered hydrophobic-polar patterning. A When all e positions are mutated to Val, departing from the canonical 3–4 repeat and creating a 3-3-1 hydrophobic repeat, the resulting sequence gives a parallel tetramer [15]. B When all g positions are substituted with either Val or Ala, also producing a 3-3-1 repeat, the result is an anti-parallel tetramer [14]. C A right-handed parallel coiled-coil tetramer [18]. D A parallel heptamer is formed when both e and g positions of GCN4 are substituted with Ala [19]. E–F A coiled coil with phenylalanine at all a and d positions folds as a parallel pentamer (E), while if just one of these phenylalanines is substituted by methionine the resulting structure is a tetramer (F) [20]