A survey of lambda repressor fragments from two-state to downhill folding.
We survey the two-state to downhill folding transition by examining 20 lambda(6-85)* mutants that cover a wide range of stabilities and folding rates. We investigated four new lambda(6-85)* mutants designed to fold especially rapidly. Two were engineered using the core remodeling of Lim and Sauer, and two were engineered using Ferreiro et al.'s frustratometer. These proteins have probe-dependent melting temperatures as high as 80 degrees C and exhibit a fast molecular phase with the characteristic temperature dependence of the amplitude expected for downhill folding. The survey reveals a correlation between melting temperature and downhill folding previously observed for the beta-sheet protein WW domain. A simple model explains this correlation and predicts the melting temperature at which downhill folding becomes possible. An X-ray crystal structure with a 1.64-A resolution of a fast-folding mutant fragment shows regions of enhanced rigidity compared to the full wild-type protein.
Center for Biophysics and Computational Biology, University of Illinois, Urbana, IL 61801, USA.
Feng
F
Liu
Yi Gui
YG
Gao
Martin
M
Gruebele
D001435:Bacteriophages; D018360:Crystallography, X-Ray; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013816:Thermodynamics; D054334:Viral Regulatory and Accessory Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D012097:Repressor Proteins; D054334:Viral Regulatory and Accessory Proteins; C016649:phage repressor proteins