AN AUTONOMOUS FOLDING UNIT MEDIATES THE ASSEMBLY OF 2-STRANDED COILEDCOILS

Subunit oligomerization of many proteins is mediated by coiled-coil do mains. Although the basic features contributing to the thermodynamic s tability of coiled coils are well understood, the mechanistic details of their assembly have not yet been dissected. Here we report a 13-res idue sequence pattern that occurs with limited sequence variations in many two-stranded coiled coils and that is absolutely required for the assembly of the Dictyostelium discoideum actin-bundling protein corte xillin I and the yeast transcriptional activator GCN4. The functional relationship between coiled coil ''trigger'' sequences was manifested by replacing the intrinsic trigger motif of GCN4 with the related sequ ence from cortexillin I. We demonstrate that these trigger sequences r epresent autonomous helical folding units that, in contrast to arbitra rily chosen heptad repeats, can mediate coiled-coil formation. Aside f rom being of general interest for protein folding, trigger motifs shou ld be of particular importance in the protein de novo design.