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The push-and-pull hypothesis in protein unfolding, misfolding and aggregation
Guilherme A P de Oliveira1, Jerson L Silva1
1Programa de Biologia Estrutural, Instituto de Bioquímica Médica Leopoldo de Meis, Instituto Nacional de Biologia Estrutural e Bioimagem, Centro Nacional de Ressonância Magnética Nuclear Jiri Jonas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Biophysical Chemistry
|April 6, 2017
Summary
Researchers visualized dry molten-globule states in proteins using biophysical methods. A new hypothesis explains how urea and pressure affect protein structures, with implications for diseases like protein misfolding.
Area of Science:
- Protein biophysics and structural biology.
- Investigating protein folding dynamics and conformational states.
Background:
- Proteins can adopt intermediate states during folding and unfolding.
- Molten-globule states represent a key transient structure between folded and unfolded forms.
- Understanding these states is crucial for comprehending protein function and dysfunction.
Purpose of the Study:
- To visualize and characterize dry molten-globule states in proteins.
- To elucidate the mechanisms by which urea and high pressure affect protein structures.
- To explore the physiological and pathological relevance of molten-globule states.
Main Methods:
- Utilizing a combination of small angle X-ray scattering (SAXS) and nuclear magnetic resonance (NMR) spectroscopy.
- Applying biophysical and structural techniques to observe protein conformational changes.
- Employing destabilizing agents like urea and high pressure.
Main Results:
- Successfully visualized protein species in dry molten-globule states.
- Observed a progression from dry-globule to wet-globule and finally to unfolded states.
- Developed a 'push-and-pull' hypothesis to differentiate urea and high-pressure effects on protein structure.
Conclusions:
- Dry molten-globule states are observable and distinct protein conformations.
- The 'push-and-pull' hypothesis provides a novel framework for understanding protein denaturation.
- Molten-globule states may play significant roles in protein misfolding diseases.