A Survey of λ Repressor Fragments from Two-State to Downhill Folding

Feng Liu, Yi Gui Gao, Martin Gruebele

Research output: Contribution to journalArticlepeer-review


We survey the two-state to downhill folding transition by examining 20 λ6-85* mutants that cover a wide range of stabilities and folding rates. We investigated four new λ6-85* 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 β-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-Å resolution of a fast-folding mutant fragment shows regions of enhanced rigidity compared to the full wild-type protein.

Original languageEnglish (US)
Pages (from-to)789-798
Number of pages10
JournalJournal of Molecular Biology
Issue number3
StatePublished - Apr 2 2010


  • CD
  • cold denaturation
  • fluorescence
  • heat denaturation
  • temperature jump

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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