Proteins with H-bond packing defects are highly interactive with lipid bilayers: Implications for amyloidogenesis
- 18 February 2003
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 100 (5) , 2391-2396
- https://doi.org/10.1073/pnas.0335642100
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.Keywords
This publication has 30 references indexed in Scilit:
- Solid-State NMR Investigations of Peptide−Lipid Interaction and Orientation of a β-Sheet Antimicrobial Peptide, ProtegrinBiochemistry, 2002
- Mapping the core of the β2-microglobulin amyloid fibril by H/D exchangeNature Structural & Molecular Biology, 2002
- Effect of Association State and Conformational Stability on the Kinetics of Immunoglobulin Light Chain Amyloid Fibril Formation at Physiological pHPublished by Elsevier ,2002
- The solution structure of human β2‐microglobulin reveals the prodromes of its amyloid transitionProtein Science, 2002
- Characterization of the structure and dynamics of amyloidogenic variants of human lysozyme by NMR spectroscopyProtein Science, 2001
- Characterization of the structure and dynamics of amyloidogenic variants of human lysozyme by NMR spectroscopyProtein Science, 2001
- Use of Attenuated Total Internal Reflection Fourier Transform Infrared Spectroscopy To Investigate Interactions between Mytilus edulis Foot Proteins at a SurfaceLangmuir, 2001
- Instability, unfolding and aggregation of human lysozyme variants underlying amyloid fibrillogenesisNature, 1997
- Review of new experimental techniques for investigating random sequential adsorptionJournal of Statistical Physics, 1993
- Influence of water structure and of hydrophobic interactions on the strength of side‐chain hydrogen bonds in proteinsBiopolymers, 1963