COILED-COIL ASSEMBLY BY PEPTIDES WITH NON-HEPTAD SEQUENCE MOTIFS

Background: The seven-residue heptad repeat is the accepted hallmark o f coiled coils. In extended filamentous proteins, however, contiguous patterns of heptads are often disrupted by 'skips' and 'stammers'. The structural consequences and roles of these digressions are not unders tood. Results: In a cytoskeleton protein from Giardia lamblia, heptads flank eleven-residue units (hendecads) to give a 7-11-7 motif that do minates the sequence. Synthetic peptides made to the consensus sequenc e of this motif fold in solution to fully helical, parallel dimers. Bo th the sequence pattern and these experimental data are consistent wit h the coiled-coil model, We note that breaks in other extended coiled coils can also be reconciled by hendecad insertions, Conclusions: The heptad paradigm for the coiled coil must be expanded to include hendec ads. As different combinations of heptads and hendecads will give diff erent overall sequence motifs, we propose that these provide a mechani sm to promote cognate protein pairings during the folding of extended coiled coils in the cell.