Insufficient hydrogen‐bond desolvation and prion‐related disease
Open Access
- 28 August 2002
- journal article
- priority paper
- Published by Wiley in European Journal of Biochemistry
- Vol. 269 (17) , 4165-4168
Abstract
A structuring and eventual exclusion of water surrounding backbone hydrogen bonds takes place during protein folding as hydrophobic residues cluster around such bonds. Taken as an average over all hydrogen bonds, the extent of desolvation is nearly a constant of motion, as revealed by re‐examination of the longest all‐atom trajectory with explicit solvent [Y. Duan & P. A. Kollman (1998) Science 282, 740]. Furthermore, this extent of desolvation is preserved across native soluble proteins, except for cellular prion proteins. Thus, a physico‐chemical picture of prion‐related disease emerges. The epitope for protein‐X binding, the region undergoing vast conformational change and the trigger and locker for this change are inferred from the location of under‐desolvated hydrogen bonds in the cellular prion protein.Keywords
This publication has 9 references indexed in Scilit:
- Curcumin has potent anti‐amyloidogenic effects for Alzheimer's β‐amyloid fibrils in vitroJournal of Neuroscience Research, 2004
- Time-resolved backbone desolvation and mutational hot spots in folding proteinsProteins: Structure, Function, and Bioinformatics, 2002
- Making a Network of Hydrophobic ClustersScience, 2002
- Physical reasons for the unusual α-helix stabilization afforded by charged or neutral polar residues in alanine-rich peptidesProceedings of the National Academy of Sciences, 2000
- NMR solution structure of the human prion proteinProceedings of the National Academy of Sciences, 2000
- D/H amide kinetic isotope effects reveal when hydrogen bonds form during protein folding.Nature Structural & Molecular Biology, 2000
- PrionsProceedings of the National Academy of Sciences, 1998
- Pathways to a Protein Folding Intermediate Observed in a 1-Microsecond Simulation in Aqueous SolutionScience, 1998
- Energetics of Protein Structure1995