Protein dynamics, folding and misfolding: from basic physical chemistry to human conformational diseases
- 8 June 2001
- journal article
- review article
- Published by Wiley in FEBS Letters
- Vol. 498 (2-3), 129-134
- https://doi.org/10.1016/s0014-5793(01)02491-7
Abstract
Proteins exhibit a variety of motions ranging from amino acid side-chain rotations to the motions of large domains. Recognition of their conformational flexibility has led to the view that protein molecules undergo fast dynamic interconversion between different conformational substates. This proposal has received support from a wide variety of experimental techniques and from computer simulations of protein dynamics. More recently, studies of the subunit dissociation of oligomeric proteins induced by hydrostatic pressure have shown that the characteristic times for subunit exchange between oligomers and for interconversion between different conformations may be rather slow (hours or days). In such cases, proteins cannot be treated as an ensemble of rapidly interconverting conformational substates, but rather as a persistently heterogeneous population of different long-lived conformers. This is reminiscent of the deterministic behavior exhibited by macroscopic bodies, and may have important implications for our understanding of protein folding and biological functions. Here, we propose that the deterministic behavior of proteins may be closely related to the genesis of conformational diseases, a class of pathological conditions that includes transmissible spongiform encephalopathies, Alzheimer's disease and other amyloidosis.Keywords
This publication has 46 references indexed in Scilit:
- Conformational diversity in a yeast prion dictates its seeding specificityNature, 2001
- The molecular biology of prion propagationPhilosophical Transactions Of The Royal Society B-Biological Sciences, 2001
- Evidence for the Conformation of the Pathologic Isoform of the Prion Protein Enciphering and Propagating Prion DiversityScience, 1996
- Mechanisms of Neuronal Degeneration in Alzheimer's DiseaseNeuron, 1996
- Phosphorescence Reveals a Continued Slow Annealing of the Protein Core following Reactivation of Escherichia coli Alkaline PhosphataseBiochemistry, 1995
- Kinetics versus Thermodynamics in Protein FoldingBiochemistry, 1994
- Deterministic Pressure-Induced Dissociation of Vicilin, the 7S Storage Globulin from Pea Seeds: Effects of pH and Cosolvents on Oligomer StabilityBiochemistry, 1994
- Reversible Pressure Dissociation of R17 Bacteriophage: The Physical Individuality of Virus ParticlesJournal of Molecular Biology, 1993
- Principles that Govern the Folding of Protein ChainsScience, 1973
- Does the Agent of Scrapie Replicate without Nucleic Acid ?Nature, 1967