Molecular basis of coiled-coil formation

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 f...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2007-04, Vol.104 (17), p.7062-7067
Main Authors: Steinmetz, Michel O, Jelesarov, Ilian, Matousek, William M, Honnappa, Srinivas, Jahnke, Wolfgang, Missimer, John H, Frank, Sabine, Alexandrescu, Andrei T, Kammerer, Richard A
Format: Article
Language:English
Subjects:
Amino Acid Substitution
Arginine
Basic-Leucine Zipper Transcription Factors
Biochemistry
Biological Sciences
Biophysics
DNA-Binding Proteins - chemistry
DNA-Binding Proteins - metabolism
Hydrogen-Ion Concentration
Kinetics
Leucine Zippers
Magnetic Resonance Spectroscopy
Molecules
Mutant Proteins - chemistry
Peptides - chemistry
Protein Folding
Proteins
Saccharomyces cerevisiae Proteins - chemistry
Saccharomyces cerevisiae Proteins - metabolism
Solutions
Thermodynamics
Transcription Factors - chemistry
Transcription Factors - metabolism
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0700321104