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Sequence determinants of a protein folding pathway
Chiaki Nishimura1, Michael A Lietzow, H Jane Dyson
1Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Journal of Molecular Biology
|July 12, 2005
Summary
Early hydrophobic interactions in apomyoglobin folding are driven by specific amino acid sequences. Mutating these sequences alters folding pathways and transient contacts, confirming sequence-based predictions.
Area of Science:
- Protein folding dynamics
- Biophysics
- Molecular biology
Background:
- Unfolded protein states exhibit local hydrophobic collapse and transient long-range interactions.
- These interactions often occur in sequence regions that bury significant hydrophobic surface area upon folding.
Purpose of the Study:
- To investigate the role of sequence-predicted hydrophobic surface area in initiating protein folding.
- To understand how local sequence properties influence early hydrophobic interactions and subsequent folding pathways.
Main Methods:
- Preparation and characterization of apomyoglobin mutants with altered buried surface area.
- Quench-flow experiments to analyze protein folding pathways.
- Spin label experiments to probe transient long-range contacts in unfolded states.
Main Results:
- Mutant apomyoglobin folding behavior aligned with predictions based on altered buried surface area.
- Transient long-range contacts in wild-type apomyoglobin were disrupted in mutants.
- New contacts formed in mutants between regions with increased predicted buried surface area.
Conclusions:
- Specific amino acid sequence groupings dictate early hydrophobic interactions in apomyoglobin folding.
- These sequence-driven interactions are critical for determining the overall folding pathway.
- Predicting buried surface area from amino acid sequence can forecast early folding events.