After having focussed on the β-sheet in the Editorial (see pages 749–750), it would be difficult — nearly impossible, in fact — to further discuss some of the latest results in biomolecular structural biology presented at the recent American Crystallographic Association Annual Meeting without mentioning the α-helix, very much the `first among equals' of protein secondary structure. Perhaps the most apposite example was provided by P. Burkhard (University of Basel, Switzerland) who reported on the structure determination of the 190 Å long α-helical, two-stranded, right-handed coiled-coil rod domain (Ir) from cortexillin I, an actin-bundling protein from Dictyostelium discoideum (shown below). This is the longest structure of a coiled coil reported to date, soundly beating the 39-residue long cFos-cJun bZIP leucine zipper.

Cortexillin I is comprised of a globular head domain and the rod, or oligomerization domain, the later of which consists of 18 heptad repeats. It is common knowledge that fragments of coiled coil domains very often do not associate into coiled coils, indicating that the heptad repeats are not sufficient to drive assembly of the quaternary conformation. What, then, was the secret of the success of the Ir structure determination? The rod domain includes a 13-residue `trigger site' (space filling format above) that has been shown to be necessary for coiled coil assembly and, indeed, has been characterized as an autonomous folding unit. Biochemical experiments have suggested that electrostatic interactions are a critical component of the trigger site's structure (Steinmetz, M.O. et. al. EMBO J. 17, 1883–1891; 1998). These observations are further supported by the structure, which shows that all 16 intramolecular salt bridges seen in the Ir structure are formed at the trigger site. A consensus sequence for the trigger site has been identified in other coiled coils and the Ir trigger sequence has been shown to function in the context of the GCN4 coiled coil (Krammerer, R.A. et al., Proc.Natl. Acad. Sci. USA in the press), suggesting that this is a general feature of coiled coil assembly.

GR