Β-Pleated SHEET FIBRILS a COMPARISON OF NATIVE AMYLOID WITH SYNTHETIC PROTEIN FIBRILS

Glenner, George G.; Eanes, E. D.; Bladen, Howard A.; Linke, R. P.; Termine, John D.

doi:10.1177/22.12.1141

Cited by 285 publications

(169 citation statements)

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“…In fact, QHF-litho failed to even bind CR, and the dye was washed off readily from samples prepared from fibril pellets after centrifugation. The same result was obtained when we examined the CR absorption spectra in the presence of QHF-litho or glucagon fibrils that have been shown previously (20) to be amyloid in nature. Whereas glucagon fibrils characteristically increased the CR absorption signal at 540 nm, no such effect could be detected for QHF-litho (Fig.…”

Section: Lithostathine Fibrils Did Not Possess the Classical Propertiessupporting

confidence: 54%

Lithostathine Quadruple-helical Filaments Form Proteinase K-resistant Deposits in Creutzfeldt-Jakob Disease

Laurine

Grégoire

Fändrich³

et al. 2003

Journal of Biological Chemistry

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Autocatalytic cleavage of lithostathine leads to the formation of quadruple-helical fibrils (QHF-litho) that are present in Alzheimer's disease. Here we show that such fibrils also occur in Creutzfeldt-Jakob and Gerstmann-Strä ussler-Scheinker diseases, where they form protease-K-resistant deposits and co-localize with amyloid plaques formed from prion protein. Lithostathine does not appear to change its native-like, globular structure during fibril formation. However, we obtained evidence that a cluster of six conserved tryptophans, positioned around a surface loop, could act as a mobile structural element that can be swapped between adjacent protein molecules, thereby enabling the formation of higher order fibril bundles. Despite their association with these clinical amyloid deposits, QHF-litho differ from typical amyloid fibrils in several ways, for example they produce a different infrared spectrum and cannot bind Congo Red, suggesting that they may not represent amyloid structures themselves. Instead, we suggest that lithostathine constitutes a novel component decorating disease-associated amyloid fibrils. Interestingly, [6,6 ]bibenzothiazolyl-2,2 -diamine, an agent found previously to disrupt aggregates of huntingtin associated with Huntington's disease, can dissociate lithostathine bundles into individual protofilaments. Disrupting QHF-litho fibrils could therefore represent a novel therapeutic strategy to combat clinical amyloidoses.

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Section: Lithostathine Fibrils Did Not Possess the Classical Propertiessupporting

confidence: 54%

Lithostathine Quadruple-helical Filaments Form Proteinase K-resistant Deposits in Creutzfeldt-Jakob Disease

Laurine

Grégoire

Fändrich³

et al. 2003

Journal of Biological Chemistry

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“…Furthermore, spectroscopic and X-ray ¢bril di¡raction studies show that all amyloid ¢brils contain a major component of cross-b secondary structure (Glenner et al 1974). A recent di¡raction study of a number of di¡erent ex vivo and synthetic amyloid ¢brils con¢rmed that all share a common core structure consisting of antiparallel b-strands forming sheets lying with their long axes perpendicular to the ¢bril long axis .…”

Section: Amyloid Fibrillogenesismentioning

confidence: 99%

Pathogenesis, diagnosis and treatment of systemic amyloidosis

Pepys

2001

Phil. Trans. R. Soc. Lond. B

201

156

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Amyloidosis is a disorder of protein folding in which normally soluble proteins are deposited as abnormal, insoluble ¢brils that disrupt tissue structure and cause disease. Although about 20 di¡erent unrelated proteins can form amyloid ¢brils in vivo, all such ¢brils share a common cross-b core structure. Some natural wild-type proteins are inherently amyloidogenic, form ¢brils and cause amyloidosis in old age or if present for long periods at abnormally high concentration. Other amyloidogenic proteins are acquired or inherited variants, containing amino-acid substitutions that render them unstable so that they populate partly unfolded states under physiological conditions, and these intermediates then aggregate in the stable amyloid fold. In addition to the ¢brils, amyloid deposits always contain the non-¢brillar pentraxin plasma protein, serum amyloid P component (SAP), because it undergoes speci¢c calcium-dependent binding to amyloid ¢brils. SAP contributes to amyloidogenesis, probably by stabilizing amyloid ¢brils and retarding their clearance. Radiolabelled SAP is an extremely useful, safe, speci¢c, non-invasive, quantitative tracer for scintigraphic imaging of systemic amyloid deposits. Its use has demonstrated that elimination of the supply of amyloid ¢bril precursor proteins leads to regression of amyloid deposits with clinical bene¢t. Current treatment of amyloidosis comprises careful maintenance of impaired organ function, replacement of end-stage organ failure by dialysis or transplantation, and vigorous e¡orts to control underlying conditions responsible for production of ¢bril precursors. New approaches under development include drugs for stabilization of the native fold of precursor proteins, inhibition of ¢brillogenesis, reversion of the amyloid to the native fold, and dissociation of SAP to accelerate amyloid ¢bril clearance in vivo.

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“…The myoglobin fragment MYO(101-118) and serum amyloid A (SAA)1.1 (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21) were obtained from Jerini (Berlin). Transthyretin was a gift from M. Krebs and C. Robinson, (University of Cambridge, Cambridge, U.K.) The coding region of full-length murine SAA1.1 was cloned in fusion to the gene of the maltose-binding protein in the pMAL-c2X vector (NEB, Beverly, MA) and separated by a cleavage site for tobacco etch virus protease.…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

“…Amyloid fibrils differ from ordinary protein fibrils by a conserved structural motif that encompasses ␤-sheets within a cross-␤ arrangement (4,5). At present, Ϸ30 nonhomologous polypeptide sequences are known to form such fibrils inside the body (3), but the basic ability to adopt this type of structure is common to many other, if not all, polypeptide sequences (1,4,(6)(7). Such observations promoted the view that amyloid fibrils arise primarily from an intrinsic property of the chiral polypeptide main chain that is often suppressed in nature by unfavorable physicochemical conditions, side-chain arrangements, or evolutionary adaptations (1,(6)(7).…”

mentioning

confidence: 99%

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Raft lipids as common components of human extracellular amyloid fibrils

Gellermann

Appel

Tannert

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

190

163

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Amyloid fibrils are fibrillar polypeptide aggregates from several degenerative human conditions, including Alzheimer's and Creutzfeldt-Jakob diseases. Analysis of amyloid fibrils derived from various human diseases (AA, ATTR, A␤2M, AL , and AL amyloidosis) shows that these are associated with a common lipid component that has a conserved chemical composition and that is specifically rich in cholesterol and sphingolipids, the major components of cellular lipid rafts. This pattern is not notably affected by the purification procedure, and no tight lipid interactions can be detected when preformed fibrils are mixed with lipids. By contrast, the early and prefibrillar aggregates formed in an AA amyloidproducing cell system interact with the raft marker ganglioside-1, and amyloid formation is impaired by addition of cholesterolreducing agents. These data suggest the existence of common cellular mechanisms in the generation of different types of clinical amyloid deposits.protein folding ͉ prion ͉ lipid rafts

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Β-Pleated SHEET FIBRILS a COMPARISON OF NATIVE AMYLOID WITH SYNTHETIC PROTEIN FIBRILS

Cited by 285 publications

References 0 publications

Lithostathine Quadruple-helical Filaments Form Proteinase K-resistant Deposits in Creutzfeldt-Jakob Disease

Lithostathine Quadruple-helical Filaments Form Proteinase K-resistant Deposits in Creutzfeldt-Jakob Disease

Pathogenesis, diagnosis and treatment of systemic amyloidosis

Raft lipids as common components of human extracellular amyloid fibrils

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