Unifying features in protein-folding mechanisms.
We compare the folding of representative members of a protein superfamily by experiment and simulation to investigate common features in folding mechanisms. The homeodomain superfamily of three-helical, single-domain proteins exhibits a spectrum of folding processes that spans the complete transition from concurrent secondary and tertiary structure formation (nucleation-condensation mechanism) to sequential secondary and tertiary formation (framework mechanism). The unifying factor in their mechanisms is that the transition state for (un)folding is expanded and very native-like, with the proportion and degree of formation of secondary and tertiary interactions varying. There is a transition, or slide, from the framework to nucleation-condensation mechanism with decreasing stability of the secondary structure. Thus, framework and nucleation-condensation are different manifestations of an underlying common mechanism.
Medical Research Council Centre for Protein Engineering, Hills Road, Cambridge CB2 2QH, United Kingdom.
Stefano
S
Gianni
Nicholas R
NR
Guydosh
Faaizah
F
Khan
Teresa D
TD
Caldas
Ugo
U
Mayor
George W N
GW
White
Mari L
ML
DeMarco
Valerie
V
Daggett
Alan R
AR
Fersht
D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D020598:Proto-Oncogene Proteins c-myb / Q000737:chemistry; D000089804:Shelterin Complex; D012984:Software; D034501:Telomere-Binding Proteins / Q000737:chemistry; D035321:Telomeric Repeat Binding Protein 1 / Q000737:chemistry; D013696:Temperature; D013816:Thermodynamics; D014508:Urea / Q000494:pharmacology
D020598:Proto-Oncogene Proteins c-myb; D000089804:Shelterin Complex; C440809:TERF2IP protein, human; D034501:Telomere-Binding Proteins; D035321:Telomeric Repeat Binding Protein 1; D014508:Urea