title: 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.affiliation: Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637, USA. ariel@uchicago.edu
authors.forename: Ariel
authors.initials: A
authors.lastname: Fernández
authors.forename: R Stephen
authors.initials: RS
authors.lastname: Berry
mesh_terms: D000327:Adsorption; D020816:Amino Acid Motifs; D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D002462:Cell Membrane / Q000378:metabolism; D019992:Databases as Topic; D006801:Humans; D006860:Hydrogen Bonding; D007700:Kinetics; D008051:Lipid Bilayers; D008958:Models, Molecular; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry; D013997:Time Factors
chemical_list: D000682:Amyloid; D008051:Lipid Bilayers; D011506:Proteins