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Related Experiment Videos

Watching proteins fold one molecule at a time.

Elizabeth Rhoades1, Eugene Gussakovsky, Gilad Haran

  • 1Department of Chemical Physics, Weizmann Institute of Science, Rehovot 76100, Israel.

Proceedings of the National Academy of Sciences of the United States of America
|March 4, 2003
PubMed
Summary

Single-molecule studies reveal protein folding uses diverse pathways on complex energy landscapes. This research provides direct evidence for heterogeneous protein folding dynamics, challenging previous assumptions.

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Area of Science:

  • Biophysics
  • Molecular Biology
  • Biochemistry

Background:

  • Theoretical models propose protein folding occurs via multiple pathways on rugged energy landscapes.
  • Understanding these pathways is crucial for comprehending protein function and misfolding diseases.

Purpose of the Study:

  • To provide direct experimental evidence for heterogeneous protein folding pathways.
  • To investigate the dynamics of protein conformational changes at the single-molecule level.

Main Methods:

  • Utilized a novel immobilization technique using surface-tethered lipid vesicles to trap single, fluorophore-labeled adenylate kinase molecules.
  • Employed fluorescence resonance energy transfer (FRET) between two labels to monitor conformational fluctuations at the thermodynamic midtransition point.

Related Experiment Videos

  • Analyzed step sizes and timescales of folding/unfolding transitions in fluorescence intensity time traces.

    • Main Results:

    • Observed a broad distribution of step sizes in FRET efficiency, peaking at low values, indicating a preference for small-step conformational changes.
    • Found a distributed timescale for transitions, with some slowest transitions exceeding 1 second.
    • Demonstrated heterogeneous folding pathways through single-molecule conformational dynamics.

    Conclusions:

    • Single-molecule studies confirm heterogeneous protein folding pathways.
    • Small-step motions and slow conformational dynamics are significant features of the protein folding energy landscape.
    • Correlated, non-Markovian dynamics may play a critical role in protein folding processes.