An experimental survey of the transition between two-state and downhill protein folding scenarios

Feng Liu, Deguo Du, Amelia A. Fuller, Jennifer E. Davoren, Peter Wipf, Jeffery W. Kelly, Martin Gruebele

Research output: Contribution to journalArticlepeer-review

Abstract

A kinetic and thermodynamic survey of 35 WW domain sequences is used in combination with a model to discern the energetic requirements for the transition from two-state folding to downhill folding. The sequences used exhibit a 600-fold range of folding rates at the temperature of maximum folding rate. Very stable proteins can achieve complete downhill folding when the temperature is lowered sufficiently below the melting temperature, and then at even lower temperatures they become two-state folders again because of cold denaturation. Less stable proteins never achieve a sufficient bias to fold downhill because of the onset of cold denaturation. The model, considering both heat and cold denaturation, reveals that to achieve incipient downhill folding (barrier <3 RT) or downhill folding (no barrier), the WW domain average melting temperatures have to be >50°C for incipient downhill folding and >90°C for downhill folding.

Original languageEnglish (US)
Pages (from-to)2369-2374
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number7
DOIs
StatePublished - Feb 19 2008

Keywords

  • Activated rate
  • Alkene peptide isosteres
  • Molecular rate
  • Speed limit
  • Stability

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'An experimental survey of the transition between two-state and downhill protein folding scenarios'. Together they form a unique fingerprint.

Cite this