The hydrophobic a and d core residues also contribute significantly to oligomerization-state specificity of coiled coils. This is exemplified by the trimerization motif that specifies a three-stranded, parallel topology of coiled-coil domains. The trimerization driving force of the motif can be explained by optimal side chain�Cside chain interactions whereby the strictly conserved arginine and glutamate residues form a distinct, bifurcated, interhelical salt-bridge network and participate in the formation of the hydrophobic core by establishing tight packing interactions to the neighbouring residues at the a and d positions through their aliphatic moieties. An open issue is that the presence of a specific oligomerizationstate determinant frequently does not correlate with the corresponding coiled-coil topology. Although the trimerization motif RhxxhE is predominantly found in protein families harboring parallel, addition chronic accumulation triggers reduction sst level three-stranded coiled-coil domains, it is also present in some dimers and antiparallel trimers. We have recently addressed this issue and identified a general link between coiledcoil oligomerization-state specificity and trigger-sequence function. By using the archetype coiled-coil domain of the yeast transcriptional activator GCN4 as a model system, we showed that trimer-specific oligomerization-state determinants such as the trimerization motif or isoleucine residues at the heptad-repeat a and d positions switch the peptide’s topology from a dimer to a trimer only when inserted into the trigger sequence. We successfully confirmed our results in two other, unrelated coiledcoil dimers, ATF1 and cortexillin-1. Because of its substantial size of 18 continuous heptad repeats, we used a combination of trimerspecific determinants to switch the cortexillin-1 coiled coil from a dimer to a trimer. Accordingly, we rationally substituted residues to complement two ideal trimerizer motifs of the type R-IxxIE and introduced one additional hydrophobic core isoleucine residue in the trigger sequence of the cortexillin-1 coiled coil. These substitutions were designed to span the entire trigger sequence. Because high-resolution structural information could not be obtained for the full-length Cort-Ir-M1 trimer, the aim of the present study was to perform a detailed structural characterization of two fragments spanning the trigger sequence of the trimeric Cort-Ir-M1 coiled coil using circular dichroism, anatytical ultracentrifugation and x-ray crystallography. We provide the structural basis for the observed switch in oligomerization state of the cortexillin-1 coiled coil from a dimer to a trimer, and therefore provide further evidence for the general link between coiled-coil oligomerization-state specificity and trigger-sequence function. The dissociation constant of GFP-Cort-Ir-M1-short1 was calculated using a two-state-model, assuming only monomeric and trimeric species as there was no experimental evidence for the presence of significant amounts of dimers.