A Survey of Lambda Repressor Fragments from Two-state to Downhill Folding
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Molecular Biology
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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.
Pollenz R, Barnhill K, Biggs A, Bland J, Carter V, Chase M G3 (Bethesda). 2024; 14(5).
PMID: 38456318 PMC: 11075535. DOI: 10.1093/g3journal/jkae049.
Prigozhin M, Zhang Y, Schulten K, Gruebele M, Pogorelov T Proc Natl Acad Sci U S A. 2019; 116(12):5356-5361.
PMID: 30837309 PMC: 6431218. DOI: 10.1073/pnas.1814927116.
Hanazono Y, Takeda K, Miki K FEBS Open Bio. 2018; 8(8):1312-1321.
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Chao S, Schafer J, Gruebele M Biochemistry. 2017; 56(42):5671-5678.
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Malhotra P, Udgaonkar J Protein Sci. 2016; 25(11):1924-1941.
PMID: 27522064 PMC: 5079258. DOI: 10.1002/pro.3015.