Proteins with hydrogen-bond packing defects are highly interactive with lipid bilayers: implications for amyloidogenesis

ARIEL FERNANDEZ; R. STEPHEN BERRY

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

NATL ACAD SCIENCES

Año: 2003 vol. 100 p. 2391 - 2396

0027-8424

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 proposi- tion that soluble proteins with amyloidogenic propensity and membrane proteins share a pervasive building motif: the under-wrapped H bonds. Whereas in membrane proteins, this motif does not signal a structural vulnerability, in soluble proteins it is responsible for their reactivity.