Direct observation of fast protein conformational switching

Haruto Ishikawa, Kyungwon Kwak, Jean K. Chung, Seongheun Kim, Michael D. Fayer

Research output: Contribution to journalArticlepeer-review

114 Citations (Scopus)


Folded proteins can exist in multiple conformational substates. Each substate reflects a local minimum on the free-energy landscape with a distinct structure. By using ultrafast 2D-IR vibrational echo chemical-exchange spectroscopy, conformational switching between two well defined substates of a myoglobin mutant is observed on the ≈50-ps time scale. The conformational dynamics are directly measured through the growth of cross peaks in the 2D-IR spectra of CO bound to the heme active site. The conformational switching involves motion of the distal histidine/E helix that changes the location of the imidazole side group of the histidine. The exchange between substates changes the frequency of the CO, which is detected by the time dependence of the 2D-IR vibrational echo spectrum. These results demonstrate that interconversion between protein conformational substates can occur on very fast time scales. The implications for larger structural changes that occur on much longer time scales are discussed.

Original languageEnglish
Pages (from-to)8619-8624
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number25
Publication statusPublished - 2008 Jun 24
Externally publishedYes


  • Multidimensional IR spectroscopy
  • Myoglobin
  • Protein dynamics
  • Protein structural change
  • Ultrafast IR

ASJC Scopus subject areas

  • General


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