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Title: A Survey of lamba Repressor Fragments from Two-State to to Downhill Folding

Journal Article · · Journal of Molecular Biology

We survey the two-state to downhill folding transition by examining 20 {lambda}{sub 6-85}* mutants that cover a wide range of stabilities and folding rates. We investigated four new {lambda}{sub 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 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-{angstrom} resolution of a fast-folding mutant fragment shows regions of enhanced rigidity compared to the full wild-type protein.

Research Organization:
Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source
Sponsoring Organization:
DOE - OFFICE OF SCIENCE
DOE Contract Number:
DE-AC02-98CH10886
OSTI ID:
1019812
Report Number(s):
BNL-95658-2011-JA; JMOBAK; TRN: US201115%%448
Journal Information:
Journal of Molecular Biology, Vol. 397, Issue 3; ISSN 0022-2836
Country of Publication:
United States
Language:
English