Annular protofibrils area structurally and functionally distinct type of amyloid oligomer

Rakez Kayed, Anna Pensalfini, Larry Margol, Yuri Sokolov, Floyd Sarsoza, Elizabeth Head, James Hall, Charles Glabe

Research output: Contribution to journalArticle

223 Citations (Scopus)

Abstract

Amyloid oligomers are believed to play causal roles in several types of amyloid-related neurodegenerative diseases. Several different types of amyloid oligomers have been reported that differ in morphology, size, or toxicity, raising the question of the pathological significance and structural relationships between different amyloid oligomers. Annular protofibrils (APFs) have been described in oligomer preparations of many different amyloidogenic proteins and peptides as ring-shaped or pore-like structures. They are interesting because their pore-like morphology is consistent with numerous reports of membrane-permeabilizing activity of amyloid oligomers. Here we report the preparation of relatively homogeneous preparations of APFs and an antiserum selective for APFs (αAPF) compared with prefibrillar oligomers (PFOs) and fibrils. PFOs appear to be precursors for APF formation, which form in high yield after exposure to a hydrophobic-hydrophilic interface. Surprisingly, preformed APFs do not permeabilize lipid bilayers, unlike the precursor PFOs. APFs display a conformation-dependent, generic epitope that is distinct from that of PFOs and amyloid fibrils. Incubation of PFOs with phospholipids vesicles results in a loss of PFO immunoreactivity with a corresponding increase in αAPF immunoreactivity, suggesting that lipid vesicles catalyze the conversion of PFOs into APFs. The annular anti-protofibril antibody also recognizes heptameric α-hemolysin pores, but not monomers, suggesting that the antibody recognizes an epitope that is specific for a β barrel structural motif.

Original languageEnglish (US)
Pages (from-to)4230-4237
Number of pages8
JournalJournal of Biological Chemistry
Volume284
Issue number7
DOIs
StatePublished - Feb 13 2009
Externally publishedYes

Fingerprint

Oligomers
Amyloid
Epitopes
Amyloidogenic Proteins
Hemolysin Proteins
Lipid Bilayers
Neurodegenerative Diseases
Immune Sera
Anti-Idiotypic Antibodies
Phospholipids
Neurodegenerative diseases
Lipids
Peptides
Lipid bilayers
Membranes
Antibodies
Toxicity
Conformations
Monomers

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Annular protofibrils area structurally and functionally distinct type of amyloid oligomer. / Kayed, Rakez; Pensalfini, Anna; Margol, Larry; Sokolov, Yuri; Sarsoza, Floyd; Head, Elizabeth; Hall, James; Glabe, Charles.

In: Journal of Biological Chemistry, Vol. 284, No. 7, 13.02.2009, p. 4230-4237.

Research output: Contribution to journalArticle

Kayed, R, Pensalfini, A, Margol, L, Sokolov, Y, Sarsoza, F, Head, E, Hall, J & Glabe, C 2009, 'Annular protofibrils area structurally and functionally distinct type of amyloid oligomer', Journal of Biological Chemistry, vol. 284, no. 7, pp. 4230-4237. https://doi.org/10.1074/jbc.M808591200
Kayed, Rakez ; Pensalfini, Anna ; Margol, Larry ; Sokolov, Yuri ; Sarsoza, Floyd ; Head, Elizabeth ; Hall, James ; Glabe, Charles. / Annular protofibrils area structurally and functionally distinct type of amyloid oligomer. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 7. pp. 4230-4237.
@article{f6473cc4f82c4e369b3efdae486b5312,
title = "Annular protofibrils area structurally and functionally distinct type of amyloid oligomer",
abstract = "Amyloid oligomers are believed to play causal roles in several types of amyloid-related neurodegenerative diseases. Several different types of amyloid oligomers have been reported that differ in morphology, size, or toxicity, raising the question of the pathological significance and structural relationships between different amyloid oligomers. Annular protofibrils (APFs) have been described in oligomer preparations of many different amyloidogenic proteins and peptides as ring-shaped or pore-like structures. They are interesting because their pore-like morphology is consistent with numerous reports of membrane-permeabilizing activity of amyloid oligomers. Here we report the preparation of relatively homogeneous preparations of APFs and an antiserum selective for APFs (αAPF) compared with prefibrillar oligomers (PFOs) and fibrils. PFOs appear to be precursors for APF formation, which form in high yield after exposure to a hydrophobic-hydrophilic interface. Surprisingly, preformed APFs do not permeabilize lipid bilayers, unlike the precursor PFOs. APFs display a conformation-dependent, generic epitope that is distinct from that of PFOs and amyloid fibrils. Incubation of PFOs with phospholipids vesicles results in a loss of PFO immunoreactivity with a corresponding increase in αAPF immunoreactivity, suggesting that lipid vesicles catalyze the conversion of PFOs into APFs. The annular anti-protofibril antibody also recognizes heptameric α-hemolysin pores, but not monomers, suggesting that the antibody recognizes an epitope that is specific for a β barrel structural motif.",
author = "Rakez Kayed and Anna Pensalfini and Larry Margol and Yuri Sokolov and Floyd Sarsoza and Elizabeth Head and James Hall and Charles Glabe",
year = "2009",
month = "2",
day = "13",
doi = "10.1074/jbc.M808591200",
language = "English (US)",
volume = "284",
pages = "4230--4237",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "7",

}

TY - JOUR

T1 - Annular protofibrils area structurally and functionally distinct type of amyloid oligomer

AU - Kayed, Rakez

AU - Pensalfini, Anna

AU - Margol, Larry

AU - Sokolov, Yuri

AU - Sarsoza, Floyd

AU - Head, Elizabeth

AU - Hall, James

AU - Glabe, Charles

PY - 2009/2/13

Y1 - 2009/2/13

N2 - Amyloid oligomers are believed to play causal roles in several types of amyloid-related neurodegenerative diseases. Several different types of amyloid oligomers have been reported that differ in morphology, size, or toxicity, raising the question of the pathological significance and structural relationships between different amyloid oligomers. Annular protofibrils (APFs) have been described in oligomer preparations of many different amyloidogenic proteins and peptides as ring-shaped or pore-like structures. They are interesting because their pore-like morphology is consistent with numerous reports of membrane-permeabilizing activity of amyloid oligomers. Here we report the preparation of relatively homogeneous preparations of APFs and an antiserum selective for APFs (αAPF) compared with prefibrillar oligomers (PFOs) and fibrils. PFOs appear to be precursors for APF formation, which form in high yield after exposure to a hydrophobic-hydrophilic interface. Surprisingly, preformed APFs do not permeabilize lipid bilayers, unlike the precursor PFOs. APFs display a conformation-dependent, generic epitope that is distinct from that of PFOs and amyloid fibrils. Incubation of PFOs with phospholipids vesicles results in a loss of PFO immunoreactivity with a corresponding increase in αAPF immunoreactivity, suggesting that lipid vesicles catalyze the conversion of PFOs into APFs. The annular anti-protofibril antibody also recognizes heptameric α-hemolysin pores, but not monomers, suggesting that the antibody recognizes an epitope that is specific for a β barrel structural motif.

AB - Amyloid oligomers are believed to play causal roles in several types of amyloid-related neurodegenerative diseases. Several different types of amyloid oligomers have been reported that differ in morphology, size, or toxicity, raising the question of the pathological significance and structural relationships between different amyloid oligomers. Annular protofibrils (APFs) have been described in oligomer preparations of many different amyloidogenic proteins and peptides as ring-shaped or pore-like structures. They are interesting because their pore-like morphology is consistent with numerous reports of membrane-permeabilizing activity of amyloid oligomers. Here we report the preparation of relatively homogeneous preparations of APFs and an antiserum selective for APFs (αAPF) compared with prefibrillar oligomers (PFOs) and fibrils. PFOs appear to be precursors for APF formation, which form in high yield after exposure to a hydrophobic-hydrophilic interface. Surprisingly, preformed APFs do not permeabilize lipid bilayers, unlike the precursor PFOs. APFs display a conformation-dependent, generic epitope that is distinct from that of PFOs and amyloid fibrils. Incubation of PFOs with phospholipids vesicles results in a loss of PFO immunoreactivity with a corresponding increase in αAPF immunoreactivity, suggesting that lipid vesicles catalyze the conversion of PFOs into APFs. The annular anti-protofibril antibody also recognizes heptameric α-hemolysin pores, but not monomers, suggesting that the antibody recognizes an epitope that is specific for a β barrel structural motif.

UR - http://www.scopus.com/inward/record.url?scp=63249103989&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=63249103989&partnerID=8YFLogxK

U2 - 10.1074/jbc.M808591200

DO - 10.1074/jbc.M808591200

M3 - Article

VL - 284

SP - 4230

EP - 4237

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 7

ER -