Open AccessInsufficient hydrogen‐bond desolvation and prion‐related disease
Author(s) -
Fernández Ariel
Publication year - 2002
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1033.2002.03116.x
Subject(s) - hydrogen bond , prion protein , folding (dsp implementation) , chemistry , protein folding , solvent , epitope , crystallography , fibril , biophysics , biochemistry , molecule , biology , disease , organic chemistry , antibody , genetics , medicine , pathology , electrical engineering , engineering
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.