Consequences of localized frustration for the folding mechanism of the IM7 protein.
In the laboratory, IM7 has been found to have an unusual folding mechanism in which an "on-pathway" intermediate with nonnative interactions is formed. We show that this intermediate is a consequence of an unusual cluster of highly frustrated interactions in the native structure. This cluster is involved in the binding of IM7 to its target, Colicin E7. Redesign of residues in this cluster to eliminate frustration is predicted by simulations to lead to faster folding without the population of an intermediate ensemble.
Sutto
Ludovico
L
Department of Physics, University of Milan, Via Celoria 16, 20133 Milan, Italy.
Lätzer
Joachim
J
Hegler
Joseph A
JA
Ferreiro
Diego U
DU
Wolynes
Peter G
PG
D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D019295:Computational Biology; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000737:chemistry* / Q000235:genetics; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D007700:Kinetics; D008958:Models, Molecular; D009154:Mutation; D017510:Protein Folding; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013816:Thermodynamics
D002352:Carrier Proteins; C509253:E colicin-binding immunity protein Im7, E coli; D029968:Escherichia coli Proteins