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Author Spotlight: Exploring Intrinsically Disordered Protein Dynamics Through NMR Relaxation Experiments
Published on: November 1, 2024
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Effect of circular permutations on transient partial unfolding in proteins
Chen Chen1, Jung-Hun Yun2, Jae-Hoon Kim2
1Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana, 47907.
Summary
Circular permutation in proteins like E. coli dihydrofolate reductase (DHFR) can alter transient partial unfolding. Modifying termini near dynamic regions significantly impacts protein stability and unfolding accessibility.
Area of Science:
- Protein biochemistry
- Structural biology
- Biophysics
Background:
- Proteins can transiently unfold, leading to misfolding and aggregation.
- Circular permutation alters sequence connectivity without changing 3D structure, potentially affecting unfolding energetics.
Purpose of the Study:
- Investigate how circular permutation impacts transient partial unfolding in proteins.
- Utilize Escherichia coli dihydrofolate reductase (DHFR) as a model system.
- Determine the effect of new N-termini placement on protein stability and unfolding.
Main Methods:
- Constructed three circular permutants of DHFR (CP18, CP37, CP87).
- Probed transient partial unfolding using native-state proteolysis.
- Analyzed the stability of native and partially unfolded forms.
Main Results:
- CP18 showed stability similar to wild-type DHFR, indicating minimal impact of termini in dynamic regions.
- CP37 exhibited increased accessibility of the partially unfolded form, suggesting promotion of unfolding near dynamic regions.
- CP87 displayed destabilized native and unfolded forms, confirming the impact of modifications in folded regions.
Conclusions:
- Circular permutation can be used to control transient partial unfolding in proteins.
- Strategic placement of new termini influences protein stability and unfolding.
- Findings offer guidelines for designing circular permutants with controlled unfolding properties.
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