Coiled coils : electrostatics & macromolecular assemblies
The coiled coil is a common and well-studied protein-folding motif. It is based on the
seven-residue repeat abcdefg, where a and d residues are largely hydrophobic.
Structurally, coiled coils comprise two or more a-helices that are brought together with
the a and d residues packing in a well-defined manner to form a hydrophobic core.
Interhelical electrostatic interactions are frequently observed between core-flanking g
and e residues. There is debate as to whether these interactions are present solely to
confer specificity, or whether they also have a role in stabilising the structures.
A program, TRAWLER, was written to analyse the core-flanking interactions in a set of
high-resolution structural data, and designed proteins were used to investigate the role
of these interactions further. It is shown that the electrostatic interactions are stabilising
in comparison to a state where the charged residues are present but not interacting. The
strength of this stabilisation is strongly context dependent: pairs containing glutamic
acid and lysine are more stabilising when the glutamic acid is placed at g and the lysine
at e. It is proposed that this is due to the packing of these residues against the surface
presented by the core a and d residues. It is noted that previous studies using different a
residues in the core exhibit the opposite preference.
Further designs include a histidine-based switch and a series of bi-faceted coiled coils.
In the latter, coiled-coil repeats were overlaid within a sequence to produce two
oligomerisation interfaces. Such sequences are seen in natural a-sheet and a-cylinder
structures. Designed peptides were intended to form vertically staggered a-cylinders,
leading to the formation of elongated nanotubes. The behaviours of these peptides are
presented and the difficulties inherent in such designs are discussed.