Side-chain pairing preferences in the parallel coiled-coil dimer motif: Insight on ion pairing between core and flanking sites

Proteins collectively display a broad array of tertiary and quaternary structures, with many different modes of packing between neighboring secondary structure elements. Among the possibilities, the R-helical coiled coil is unusual in that it is both common and regular.1 In the simplest case, two R-helices associate side-by-side, wrapping around one another with a slight left-handed superhelical twist. A characteristic “knobs-into-holes ” interdigitation of side chains is observed at the helix-helix interface, whether the helices are parallel or antiparallel.2 The relative simplicity of this architecture has led to extensive exploration of sequence-stability relationships,3 motivated by the prospects of predicting coiled-coil structure from sequence information alone, refining computational tools, and using coiled coils as building blocks in rational protein design and synthetic biology.4 Although some principles that govern coiled-coil stability have been elucidated, our understanding remain