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Association-induced folding of globular proteins
V N Uversky1, D J Segel, S Doniach
1Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA. uversky@sun.ipr.serpukhov.su
Summary
Protein aggregation during refolding can surprisingly lead to soluble, native-like structures. This study demonstrates that associated partially folded intermediates can gain significant secondary structure and globularity.
Area of Science:
- Biochemistry
- Protein Folding Dynamics
- Structural Biology
Background:
- Protein misfolding and aggregation are often considered detrimental to proper protein function.
- The aggregation of partially folded intermediates is typically assumed to halt further folding processes.
Purpose of the Study:
- To investigate the role of partially folded intermediate aggregation in protein refolding.
- To determine if aggregation can lead to structures with native-like properties.
Main Methods:
- Studying staphylococcal nuclease partially folded intermediates.
- Utilizing small-angle X-ray scattering (SAXS) to analyze protein structure.
- Measuring secondary structure content and globularity in aggregated states.
Main Results:
- Partial folding intermediates can form soluble aggregates under specific conditions (high protein or salt concentrations).
- Secondary structure content doubled in these soluble aggregates compared to monomeric intermediates.
- Increased globularity was observed in the associated states, indicating more compact structures.
Conclusions:
- Protein aggregation of partially folded intermediates is not always a dead end for folding.
- Under certain conditions, association can induce additional structure, leading to soluble, native-like aggregates.
- This finding challenges the traditional view of protein aggregation during refolding.