Steinmetz MO Jelesarov I Matousek WM Honnappa S Jahnke W Missimer JH Frank S Alexandrescu AT Kammerer RA 2007 Coiled coils have attracted considerable interest as design templates in a wide range of applications. Successful coiled-coil design strategies therefore require a detailed understanding of coiled-coil folding. One common feature shared by coiled coils is the presence of a short autonomous helical folding unit, termed "trigger sequence," that is indispensable for folding. Detailed knowledge of trigger sequences at the molecular level is thus key to a general understanding of coiled-coil formation. Using a multidisciplinary approach, we identify and characterize here the molecular determinants that specify the helical conformation of the monomeric early folding intermediate of the GCN4 coiled coil. We demonstrate that a network of hydrogen-bonding and electrostatic interactions stabilize the trigger-sequence helix. This network is rearranged in the final dimeric coiled-coil structure, and its destabilization significantly slows down GCN4 leucine zipper folding. Our findings provide a general explanation for the molecular mechanism of coiled-coil formation. application/pdf https://sonar.ch/global/documents/700 eng info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.0700321104 info:eu-repo/semantics/altIdentifier/pmid/17438295 info:eu-repo/semantics/openAccess Proceedings of the National Academy of Sciences of the United States of America. - 2007 Amino Acid Substitution Arginine Basic-Leucine Zipper Transcription Factors DNA-Binding Proteins Hydrogen-Ion Concentration Kinetics Leucine Zippers Magnetic Resonance Spectroscopy Mutant Proteins Peptides Protein Folding Saccharomyces cerevisiae Proteins Solutions Thermodynamics Transcription Factors Molecular basis of coiled-coil formation. http://purl.org/coar/resource_type/c_6501