Proteins with H-bond packing defects are highly interactive with lipid bilayers: Implications for amyloidogenesis.

Abstract:

: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.

authors

Fernández A,Berry RS

doi

10.1073/pnas.0335642100

keywords:

subject

Has Abstract

pub_date

2003-03-04 00:00:00

pages

2391-6

issue

5

eissn

0027-8424

issn

1091-6490

pii

0335642100

journal_volume

100

pub_type

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