Role of Small Oligomers on the Amyloidogenic Aggregation Free-Energy Landscape

Xianglan He, Jason T. Giurleo, David S. Talaga

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

We combine atomic-force-microscopy particle-size-distribution measurements with earlier measurements on 1-anilino-8-naphthalene sulfonate, thioflavin T, and dynamic light scattering to develop a quantitative kinetic model for the aggregation of β-lactoglobulin into amyloid. We directly compare our simulations to the population distributions provided by dynamic light scattering and atomic force microscopy. We combine species in the simulation according to structural type for comparison with fluorescence fingerprint results. The kinetic model of amyloidogenesis leads to an aggregation free-energy landscape. We define the roles of and propose a classification scheme for different oligomeric species based on their location in the aggregation free-energy landscape. We relate the different types of oligomers to the amyloid cascade hypothesis and the toxic oligomer hypothesis for amyloid-related diseases. We discuss existing kinetic mechanisms in terms of the different types of oligomers. We provide a possible resolution to the toxic oligomer-amyloid coincidence.

Original languageEnglish
Pages (from-to)134-154
Number of pages21
JournalJournal of Molecular Biology
Volume395
Issue number1
DOIs
StatePublished - 8 Jan 2010

Fingerprint

Amyloid
Atomic Force Microscopy
Poisons
Lactoglobulins
Dermatoglyphics
Particle Size
Fluorescence
Demography
Dynamic Light Scattering

Keywords

  • amyloid
  • atomic force microscopy
  • dynamic light scattering
  • fluorescence
  • protein aggregation

Cite this

@article{fdeb1517e5be42b3a901fc197fe4a5f1,
title = "Role of Small Oligomers on the Amyloidogenic Aggregation Free-Energy Landscape",
abstract = "We combine atomic-force-microscopy particle-size-distribution measurements with earlier measurements on 1-anilino-8-naphthalene sulfonate, thioflavin T, and dynamic light scattering to develop a quantitative kinetic model for the aggregation of β-lactoglobulin into amyloid. We directly compare our simulations to the population distributions provided by dynamic light scattering and atomic force microscopy. We combine species in the simulation according to structural type for comparison with fluorescence fingerprint results. The kinetic model of amyloidogenesis leads to an aggregation free-energy landscape. We define the roles of and propose a classification scheme for different oligomeric species based on their location in the aggregation free-energy landscape. We relate the different types of oligomers to the amyloid cascade hypothesis and the toxic oligomer hypothesis for amyloid-related diseases. We discuss existing kinetic mechanisms in terms of the different types of oligomers. We provide a possible resolution to the toxic oligomer-amyloid coincidence.",
keywords = "amyloid, atomic force microscopy, dynamic light scattering, fluorescence, protein aggregation",
author = "Xianglan He and Giurleo, {Jason T.} and Talaga, {David S.}",
year = "2010",
month = "1",
day = "8",
doi = "10.1016/j.jmb.2009.10.019",
language = "English",
volume = "395",
pages = "134--154",
journal = "Journal of Molecular Biology",
issn = "0022-2836",
publisher = "Academic Press Inc.",
number = "1",

}

Role of Small Oligomers on the Amyloidogenic Aggregation Free-Energy Landscape. / He, Xianglan; Giurleo, Jason T.; Talaga, David S.

In: Journal of Molecular Biology, Vol. 395, No. 1, 08.01.2010, p. 134-154.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Role of Small Oligomers on the Amyloidogenic Aggregation Free-Energy Landscape

AU - He, Xianglan

AU - Giurleo, Jason T.

AU - Talaga, David S.

PY - 2010/1/8

Y1 - 2010/1/8

N2 - We combine atomic-force-microscopy particle-size-distribution measurements with earlier measurements on 1-anilino-8-naphthalene sulfonate, thioflavin T, and dynamic light scattering to develop a quantitative kinetic model for the aggregation of β-lactoglobulin into amyloid. We directly compare our simulations to the population distributions provided by dynamic light scattering and atomic force microscopy. We combine species in the simulation according to structural type for comparison with fluorescence fingerprint results. The kinetic model of amyloidogenesis leads to an aggregation free-energy landscape. We define the roles of and propose a classification scheme for different oligomeric species based on their location in the aggregation free-energy landscape. We relate the different types of oligomers to the amyloid cascade hypothesis and the toxic oligomer hypothesis for amyloid-related diseases. We discuss existing kinetic mechanisms in terms of the different types of oligomers. We provide a possible resolution to the toxic oligomer-amyloid coincidence.

AB - We combine atomic-force-microscopy particle-size-distribution measurements with earlier measurements on 1-anilino-8-naphthalene sulfonate, thioflavin T, and dynamic light scattering to develop a quantitative kinetic model for the aggregation of β-lactoglobulin into amyloid. We directly compare our simulations to the population distributions provided by dynamic light scattering and atomic force microscopy. We combine species in the simulation according to structural type for comparison with fluorescence fingerprint results. The kinetic model of amyloidogenesis leads to an aggregation free-energy landscape. We define the roles of and propose a classification scheme for different oligomeric species based on their location in the aggregation free-energy landscape. We relate the different types of oligomers to the amyloid cascade hypothesis and the toxic oligomer hypothesis for amyloid-related diseases. We discuss existing kinetic mechanisms in terms of the different types of oligomers. We provide a possible resolution to the toxic oligomer-amyloid coincidence.

KW - amyloid

KW - atomic force microscopy

KW - dynamic light scattering

KW - fluorescence

KW - protein aggregation

UR - http://www.scopus.com/inward/record.url?scp=70450224432&partnerID=8YFLogxK

U2 - 10.1016/j.jmb.2009.10.019

DO - 10.1016/j.jmb.2009.10.019

M3 - Article

C2 - 19837085

AN - SCOPUS:70450224432

VL - 395

SP - 134

EP - 154

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

SN - 0022-2836

IS - 1

ER -