NR ANMC
AU Fernandez,A.; Berry,R.S.
TI Proteins with H-bond packing defects are highly interactive with lipid bilayers: Implications for amyloidogenesis.
QU Proceedings of the National Academy of Sciences of the United States of America 2003 Mar 4; 100(5): 2391-6
PT journal article
AB We noticed that disease-related amyloidogenic proteins and especially cellular prion proteins have the highest proportion of incompletely desolvated backbone H bonds among soluble proteins. Such bonds are vulnerable to water attack and thus represent structural weaknesses. We have measured the adsorption of proteins onto phospholipid bilayers and found a strong correlation between the extent of underwrapping of backbone H bonds in the native structure of a protein and its extent of deposition on the bilayer: the less the H bond wrapping, the higher the propensity for protein-bilayer binding. These observations support the proposition that soluble proteins with amyloidogenic propensity and membrane proteins share a pervasive building motif: the underwrapped H bonds. Whereas in membrane proteins, this motif does not signal a structural vulnerability, in soluble proteins, it is responsible for their reactivity.
MH Adsorption; Amino Acid Motifs; Amyloid/*chemistry/metabolism; Animal; Biophysics; Cell Membrane/metabolism; Databases; Human; *Hydrogen Bonding; Kinetics; *Lipid Bilayers; Models, Molecular; Protein Folding; Protein Structure, Secondary; Protein Structure, Tertiary; Proteins/chemistry; Support, U.S. Gov't, Non-P.H.S.; Time Factors
AD *Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637; Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565, Japan; and James Franck Institute and Department of Chemistry, University of Chicago, Chicago, IL 60637.
SP englisch
PO USA