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 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.
Steinmetz
Michel O
MO
Biomolecular Research, Structural Biology, Paul Scherrer Institut, CH-5232 Villigen PSI, Switzerland. michel.steinmetz@psi.ch
Jelesarov
Ilian
I
Matousek
William M
WM
Honnappa
Srinivas
S
Jahnke
Wolfgang
W
Missimer
John H
JH
Frank
Sabine
S
Alexandrescu
Andrei T
AT
Kammerer
Richard A
RA
D019943:Amino Acid Substitution; D001120:Arginine; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D016350:Leucine Zippers; D009682:Magnetic Resonance Spectroscopy; D050505:Mutant Proteins / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D017510:Protein Folding; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D012996:Solutions; D013816:Thermodynamics; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism
D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C501391:GCN4 protein, S cerevisiae; D050505:Mutant Proteins; D010455:Peptides; D029701:Saccharomyces cerevisiae Proteins; D012996:Solutions; D014157:Transcription Factors; D001120:Arginine