An autonomous folding unit mediates the assembly of two-stranded coiled coils.
Subunit oligomerization of many proteins is mediated by coiled-coil domains. Although the basic features contributing to the thermodynamic stability of coiled coils are well understood, the mechanistic details of their assembly have not yet been dissected. Here we report a 13-residue 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 cortexillin 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 sequence from cortexillin I. We demonstrate that these trigger sequences represent autonomous helical folding units that, in contrast to arbitrarily chosen heptad repeats, can mediate coiled-coil formation. Aside from being of general interest for protein folding, trigger motifs should be of particular importance in the protein de novo design.
Kammerer
R A
RA
Department of Biophysical Chemistry, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
Schulthess
T
T
Landwehr
R
R
Lustig
A
A
Engel
J
J
Aebi
U
U
Steinmetz
M O
MO
D000595:Amino Acid Sequence; D000818:Animals; D004268:DNA-Binding Proteins; D004023:Dictyostelium / Q000737:chemistry* / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry*; D008840:Microfilament Proteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D017510:Protein Folding; D011494:Protein Kinases / Q000737:chemistry*; D015800:Protozoan Proteins; D012441:Saccharomyces cerevisiae / Q000737:chemistry* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D017421:Sequence Analysis; D015534:Trans-Activators / Q000737:chemistry
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D008840:Microfilament Proteins; D015800:Protozoan Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; C101109:ctxA protein, Dictyostelium discoideum; D011494:Protein Kinases