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PABMB Lecture. Protein dynamics, folding and misfolding: from basic physical chemistry to human conformational
1Departamento de Bioquímica Médica, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, RJ 21944-590, Rio de Janeiro, Brazil. ferreira@bioqmed.ufrj.br
FEBS Letters
|June 20, 2001
Summary
Proteins can exist as long-lived, distinct forms, not just rapidly changing states. This persistent heterogeneity may explain deterministic protein behavior and link to diseases like Alzheimer's.
Area of Science:
- Biophysics
- Structural Biology
- Biochemistry
Background:
- Proteins display diverse motions, from local side-chain rotations to large domain movements.
- Traditionally, proteins are viewed as ensembles of rapidly interconverting conformational substates.
- Experimental and computational studies support the dynamic nature of protein conformations.
Purpose of the Study:
- To investigate the timescale of protein conformational interconversions.
- To explore the implications of slow conformational dynamics on protein behavior.
- To propose a link between protein deterministic behavior and conformational diseases.
Main Methods:
- Analysis of subunit dissociation in oligomeric proteins induced by hydrostatic pressure.
- Characterization of characteristic times for subunit exchange and conformational interconversion.
- Theoretical modeling of protein dynamics and heterogeneity.
Main Results:
- Studies reveal that protein subunit exchange and conformational interconversion can be slow (hours to days).
- This suggests proteins exist as persistently heterogeneous populations of long-lived conformers, not rapidly interconverting states.
- This slow dynamics resembles deterministic behavior observed in macroscopic systems.
Conclusions:
- Proteins can exhibit persistent heterogeneity with long-lived conformers.
- This deterministic behavior may be crucial for understanding protein folding and function.
- A strong correlation is proposed between this deterministic protein behavior and the pathogenesis of conformational diseases, including transmissible spongiform encephalopathies and Alzheimer's disease.