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Title: Cooperative Hydrogen Bonding in Amyloid Formation.

Abstract

The research described in this product was performed in part in the Environmental Molecular Sciences Laboratory, a national scientific user facility sponsored by the Department of Energy's Office of Biological and Environmental Research and located at Pacific Northwest National Laboratory. Amyloid diseases, including Alzheimer's and prion diseases, are each associated with unbranched protein fibrils. Each fibril is made of a particular protein, yet they share common properties. One such property is nucleation-dependent fibril growth. Monomers of amyloid-forming proteins can remain in dissolved form for long periods, before rapidly assembly into fibrils. The lag before growth has been attributed to slow kinetics of formation of a nucleus, on which other molecules can deposit to form the fibril. We have explored the energetics of fibril formation, based on the known molecular structure of a fibril-forming peptide from the yeast prion, Sup35, using both classical and quantum (density functional theory) methods. We find that the energetics of fibril formation for the first three layers are cooperative using both methods. This cooperativity is consistent with the observation that formation of amyloid fibrils involves slow nucleation and faster growth.

Authors:
; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Laboratory (PNNL), Richland, WA (US), Environmental Molecular Sciences Laboratory (EMSL)
Sponsoring Org.:
USDOE
OSTI Identifier:
921413
DOE Contract Number:
AC05-76RL01830
Resource Type:
Journal Article
Resource Relation:
Journal Name: Protein Science, 16(4):761-764; Journal Volume: 16; Journal Issue: 4
Country of Publication:
United States
Language:
English
Subject:
08 HYDROGEN; BONDING; DISEASES; FUNCTIONALS; HYDROGEN; KINETICS; MOLECULAR STRUCTURE; MONOMERS; NUCLEATION; PEPTIDES; PROTEINS; YEASTS; Environmental Molecular Sciences Laboratory

Citation Formats

Tsemekhman, Kiril L., Goldschmidt, Lukasz, Eisenberg, Dvaid, and Baker, David. Cooperative Hydrogen Bonding in Amyloid Formation.. United States: N. p., 2007. Web. doi:10.1110/ps.062609607.
Tsemekhman, Kiril L., Goldschmidt, Lukasz, Eisenberg, Dvaid, & Baker, David. Cooperative Hydrogen Bonding in Amyloid Formation.. United States. doi:10.1110/ps.062609607.
Tsemekhman, Kiril L., Goldschmidt, Lukasz, Eisenberg, Dvaid, and Baker, David. Sun . "Cooperative Hydrogen Bonding in Amyloid Formation.". United States. doi:10.1110/ps.062609607.
@article{osti_921413,
title = {Cooperative Hydrogen Bonding in Amyloid Formation.},
author = {Tsemekhman, Kiril L. and Goldschmidt, Lukasz and Eisenberg, Dvaid and Baker, David},
abstractNote = {The research described in this product was performed in part in the Environmental Molecular Sciences Laboratory, a national scientific user facility sponsored by the Department of Energy's Office of Biological and Environmental Research and located at Pacific Northwest National Laboratory. Amyloid diseases, including Alzheimer's and prion diseases, are each associated with unbranched protein fibrils. Each fibril is made of a particular protein, yet they share common properties. One such property is nucleation-dependent fibril growth. Monomers of amyloid-forming proteins can remain in dissolved form for long periods, before rapidly assembly into fibrils. The lag before growth has been attributed to slow kinetics of formation of a nucleus, on which other molecules can deposit to form the fibril. We have explored the energetics of fibril formation, based on the known molecular structure of a fibril-forming peptide from the yeast prion, Sup35, using both classical and quantum (density functional theory) methods. We find that the energetics of fibril formation for the first three layers are cooperative using both methods. This cooperativity is consistent with the observation that formation of amyloid fibrils involves slow nucleation and faster growth.},
doi = {10.1110/ps.062609607},
journal = {Protein Science, 16(4):761-764},
number = 4,
volume = 16,
place = {United States},
year = {Sun Apr 01 00:00:00 EDT 2007},
month = {Sun Apr 01 00:00:00 EDT 2007}
}