An expanded view of the protein folding landscape of PDZ domains

Research output: Contribution to journalJournal articleResearchpeer-review

Greta Hultqvist, Søren W Pedersen, Celestine N. Chi, Kristian Strømgaard, Stefano Gianni, Per Jemth

Most protein domains fold in an apparently co-operative and two-state manner with only the native and denatured states significantly populated at any experimental condition. However, the protein folding energy landscape is often rugged and different transition states may be rate limiting for the folding reaction under different conditions, as seen for the PDZ protein domain family. We have here analyzed the folding kinetics of two PDZ domains and found that a previously undetected third transition state is rate limiting under conditions that stabilize the native state relative to the denatured state. In light of these results, we have re-analyzed previous folding data on PDZ domains and present a unified folding mechanism with three distinct transition states separated by two high-energy intermediates. Our data show that sequence composition tunes the relative stabilities of folding transition states within the PDZ family, while the overall mechanism is determined by topology. This model captures the kinetic folding mechanism of all PDZ domains studied to date.
Original languageEnglish
JournalBiochemical and Biophysical Research Communications
Volume421
Issue number3
Pages (from-to)550-553
Number of pages4
ISSN0006-291X
DOIs
Publication statusPublished - 11 May 2012

    Research areas

  • Kinetics, Models, Chemical, Mutation, PDZ Domains, Protein Folding

ID: 45807323