Amyloid-β Membrane Binding and Permeabilization are Distinct Processes Influenced Separately by Membrane Charge and Fluidity

Wong, Pamela; Schauerte, Joseph A.; Wisser, Kathleen; Ding, Hao; Lee, Edgar L.; Steel, Duncan G.; Gafni, Ari

doi:10.1016/j.jmb.2008.11.060

Cited by 153 publications

(236 citation statements)

References 76 publications

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“…More likely, the results reflect strong noncovalent interactions involving regions of the denatured proteins within the lens cells, with membrane lipids or integral membrane proteins. Such a mechanism could involve partial insertion of the proteins into the membrane itself as has been shown for several peptides (Wong et al 2009). It is of interest that a protein permeability pathway that enables movement of large molecules between cells (Shestopalov and Bassnett 2003), arises in older fibre cells and this may be a function of cell membrane fusion.…”

Section: Discussionmentioning

confidence: 90%

“…Another contributing factor may be the binding of protein aggregates to the membranes of older cells. Several age-related diseases are associated with protein misfolding and aggregation (Dobson 2001) and in the case of Alzheimer's disease, a considerable body of research has focussed on the interaction of the amyloid β peptides with membranes (McLaurin and Chakrabartty 1996;Aisenbrey et al 2008;Wong et al 2009) and it is now thought that membrane binding of oligomers of these peptides may underlie their cytotoxicity (Ji et al 2001;Wong et al 2009). …”

Section: Introductionmentioning

confidence: 99%

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Tight binding of proteins to membranes from older human cells

Truscott

Comte‐Walters

Schwacke

et al. 2010

AGE

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The lens is an ideal model system for the study of macromolecular aging and its consequences for cellular function, since there is no turnover of lens fibre cells. To examine biochemical processes that take place in the lens and that may also occur in other long-lived cells, membranes were isolated from defined regions of human lenses that are synthesised at different times during life, and assayed for the presence of tightly bound cytosolic proteins using quantitative iTRAQ proteomics technology. A majority of lens beta crystallins and all gamma crystallins became increasingly membrane bound with age, however, the chaperone proteins alpha A and alpha B crystallin, as well as the thermally-stable protein, βB2 crystallin, did not. Other proteins such as brain-associated signal protein 1 and paralemmin 1 became less tightly bound in the older regions of the lens. It is evident that protein-membrane interactions change significantly with age. Selected proteins that were formerly cytosolic become increasingly tightly bound to cell membranes with age and are not removed even by treatment with 7 M urea. It is likely that such processes reflect polypeptide denaturation over time and the untoward binding of proteins to membranes may alter membrane properties and contribute to impairment of communication between older cells.

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Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Tight binding of proteins to membranes from older human cells

Truscott

Comte‐Walters

Schwacke

et al. 2010

AGE

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“…First, anionic phospholipids appear to be essential for A-beta binding and insertion. [35][36][37][38][39][40][41] Although A-beta appears to bind to neutral phospholipids, these lipids do not appear to be capable of allowing membrane insertion. This interaction is sensitive to ionic strength as would be expected for a charge-charge interaction.…”

Section: Amyloid-beta Peptidementioning

confidence: 99%

“…Contact with uncharged lipids does not appear to affect the conformation of A-beta in solution and indeed there seems to be little binding of A-beta to membranes formed from neutral phospholipids. 36 Lee et al (2002) showed that an apolipoprotein E2 which bound phosphatidylserine could competitively inhibit the toxicity of A-beta peptide. 45 A-beta has also been suggested to bind other components of the plasma membrane, including GM1 46,47 Yanagisawa et al 48 identified a unique A-beta peptide species in Alzheimer's disease brain which was characterized by strong binding to GM1.…”

Section: Amyloid-beta Peptidementioning

confidence: 99%

Amyloid Peptide Pores and the Beta Sheet Conformation

Kagan

Thundimadathil²

2010

Advances in Experimental Medicine and Biology

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O ver 20 clinical syndromes have been described as amyloid diseases. Pathologically, these illnesses are characterized by the deposition in various tissues of amorphous, Congo red staining deposits, referred to as amyloid. Under polarizing light microscopy, these deposits exhibit characteristic green birefringence. X-ray diffraction reveals cross-beta structure of extended amyloid fibrils. Although there is always a major protein in amyloid deposits, the predominant protein differs in each of the clinical syndromes. All the proteins exhibit the characteristic nonnative beta-sheet state. These proteins aggregate spontaneously into extended fibrils and precipitate out of solution. At least a dozen of these peptides have been demonstrated to be capable of channel formation in lipid bilayers and it has been proposed that this represents a pathogenic mechanism. Remarkably, the channels formed by these various peptides exhibit a number of common properties including irreversible, spontaneous insertion into membranes, production of large, heterogeneous single-channel conductances, relatively poor ion selectivity, inhibition of channel formation by Congo red and related dyes and blockade of inserted channels by zinc. In vivo amyloid peptides have been shown to disrupt intracellular calcium regulation, plasma membrane potential, mitochondrial membrane potential and function and long-term potentiation in neurons. Amyloid peptides also cause cytotoxicity. Formation of the beta sheet conformation from native protein structures can be induced by high protein concentrations, metal binding, acidic pH, amino acid mutation and interaction with lipid membranes. Most amyloid peptides interact strongly with membranes and this interaction is enhanced by conditions which favor beta-sheet formation. Formation of pores in these illnesses appears to be a spontaneous process and available evidence suggests several steps are critical. First, destabilization of the native structure and formation of the beta-sheet conformation must occur. This may occur in solution or may be facilitated by contact with lipid membranes. Oligomerization of the amyloid protein is then mediated by the beta strands. Amyloid monomers and extended fibrils appear to have little potential for toxicity whereas there is much evidence implicating amyloid oligomers of intermediate size in the pathogenesis of amyloid disease. Insertion of the oligomer appears to take place spontaneously although there may be a contribution of acidic pH and/or membrane potential. Very little is known about the structure of amyloid pores, but given that the amyloid peptides must acquire beta-sheet conformation to aggregate and polymerize, it has been hypothesized that amyloid pores may in fact be beta-sheet barrels similar to the pores formed by alpha-latrotoxin, Staphylococcal alpha-hemolysin, anthrax toxin and clostridial perfringolysin.

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“…Indeed, several studies have visualized extensive A␤ association with cell and synthetic membranes (9,10). These surfaces have been shown either to increase the degree of amyloid fibril formation or to inhibit the process, based on the charge, curvature, and composition of the lipid surface (11)(12)(13)(14). Given that the composition of the surface has a significant impact on the self-association and aggregation of A␤, it is highly likely that individual lipid molecules can also impact on these processes.…”

mentioning

confidence: 99%

Small Amphipathic Molecules Modulate Secondary Structure and Amyloid Fibril-forming Kinetics of Alzheimer Disease Peptide Aβ1–42

Ryan

Friedhuber

Lind

et al. 2012

Journal of Biological Chemistry

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Background: A␤ aggregation may be modulated by small lipid-like molecules. Results: Activators induced ␤-structure and rapid aggregation, whereas inhibitors induced ␣-helical structure and small A␤ oligomers. Conclusion: Small lipid-like molecules modulate A␤ secondary structure and self-association at stoichiometric levels. Significance: Understanding the role of small molecules and lipids in Alzheimer disease is crucial for the development of effective therapeutic targets.

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Amyloid-β Membrane Binding and Permeabilization are Distinct Processes Influenced Separately by Membrane Charge and Fluidity

Cited by 153 publications

References 76 publications

Tight binding of proteins to membranes from older human cells

Tight binding of proteins to membranes from older human cells

Amyloid Peptide Pores and the Beta Sheet Conformation

Small Amphipathic Molecules Modulate Secondary Structure and Amyloid Fibril-forming Kinetics of Alzheimer Disease Peptide Aβ1–42

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