Structural characterization of β-sheeted oligomers formed on the pathway of oxidative prion protein aggregation in vitro

Redecke, Lars; Bergen, Martin von; Clos, Joachim; Konarev, Petr V.; Svergun, Dmitri I.; Fittschen, Ursula E. A.; Broekaert, J. A. C.; Bruns, Oliver T.; Georgieva, Dessislava; Mandelkow, Eckhard; Genov, Nicolay; Betzel, Christian

doi:10.1016/j.jsb.2006.06.013

Cited by 51 publications

(64 citation statements)

References 54 publications

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“…This fact agrees with previous reports from other laboratories (25,33). With this optimized analytical method, rather confident quantification of the extent of oxidation of individual Met residues in rhPrP C by periodate was obtained.…”

Section: Mapping Met Oxidation By Mssupporting

confidence: 92%

“…The far-UV CD spectrum of Met-rhPrP C at 37°C in 10 mM Mes at pH 6.0 is identical to those previously reported (33,39), and has the 2 negative maxima at 222 and 208 nm, typical for largely ␣-helical proteins. Compared with the parent Met protein, the spectrum of the Nle-variant (Fig.…”

Section: Mapping Met Oxidation By Mssupporting

confidence: 83%

“…As expected, in the aggregation assay under oxidative conditions, the Nle-and Mox-variants were relatively insensitive to the different sodium periodate concentrations (Fig. 5B), and the observed steady increase has to be attributed to oxidative degradation of other sensitive residues, particularly Trp and Tyr (33). Thus, Nle-rhPrP C and Mox-rhPrP C proved to be suitable tools to investigate the effect of Met oxidation.…”

Section: Mapping Met Oxidation By Mssupporting

confidence: 73%

“…5B). A contribution of oxidative degradation of sensitive residues such as His, Trp, and Tyr cannot be excluded as suggested by other studies (25,33). However, the main effect has to result from the conversion of less accessible Met residues to the Met(O) form as the Nle-variant, which lacks these Met residues, shows only a slight increase in the aggregation tendency under comparative oxidative conditions.…”

Section: Oxidation Of Met Residues In Rhprp C and ␣3␤ Structural Convmentioning

confidence: 84%

“…Peroxide H 2 O 2 is routinely used in oxidation studies of many proteins including PrP C s from various organisms (25,33). However, in our hands, sodium periodate proved to be the best oxidant to generate reliable and reproducible data.…”

Section: Periodate-induced Aggregation Of Met-rhprp C As Monitored Bymentioning

confidence: 96%

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Design of anti- and pro-aggregation variants to assess the effects of methionine oxidation in human prion protein

Wolschner

Giese

Kretzschmar

et al. 2009

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

104

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Prion disease is characterized by the ␣3␤ structural conversion of the cellular prion protein (PrP C ) into the misfolded and aggregated ''scrapie'' (PrP Sc ) isoform. It has been speculated that methionine (Met) oxidation in PrP C may have a special role in this process, but has not been detailed and assigned individually to the 9 Met residues of full-length, recombinant human PrP C [rhPrP C (23-231)]. To better understand this oxidative event in PrP aggregation, the extent of periodate-induced Met oxidation was monitored by electrospray ionization-MS and correlated with aggregation propensity. Also, the Met residues were replaced with isosteric and chemically stable, nonoxidizable analogs, i.e., with the more hydrophobic norleucine (Nle) and the highly hydrophilic methoxinine (Mox). The Nle-rhPrP C variant is an ␣-helix rich protein (like MetrhPrP C ) resistant to oxidation that lacks the in vitro aggregation properties of the parent protein. Conversely, the Mox-rhPrP C variant is a ␤-sheet rich protein that features strong proaggregation behavior. In contrast to the parent Met-rhPrP C , the Nle/Moxcontaining variants are not sensitive to periodate-induced in vitro aggregation. The experimental results fully support a direct correlation of the ␣3␤ secondary structure conversion in rhPrP C with the conformational preferences of Met/Nle/Mox residues. Accordingly, sporadic prion and other neurodegenerative diseases, as well as various aging processes, might also be caused by oxidative stress leading to Met oxidation.conformational switch ͉ expanded genetic code ͉ methionine sulfoxide reductase ͉ noncanonical analogs ͉ unnatural amino acid sequence

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Section: Mapping Met Oxidation By Mssupporting

confidence: 92%

Section: Mapping Met Oxidation By Mssupporting

confidence: 83%

Section: Mapping Met Oxidation By Mssupporting

confidence: 73%

Section: Oxidation Of Met Residues In Rhprp C and ␣3␤ Structural Convmentioning

confidence: 84%

Section: Periodate-induced Aggregation Of Met-rhprp C As Monitored Bymentioning

confidence: 96%

See 3 more Smart Citations

Design of anti- and pro-aggregation variants to assess the effects of methionine oxidation in human prion protein

Wolschner

Giese

Kretzschmar

et al. 2009

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

104

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Amyloids and Protein Aggregation—Analytical Methods

Li¹,

Rahimi²,

Sinha³

et al. 2009

Encyclopedia of Analytical Chemistry

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More than 30 diseases are associated with amyloid‐forming proteins, which undergo conformational alterations and “misfolding” under particular conditions. These proteins deposit as insoluble proteinaceous aggregates generating disease‐specific histopathologic lesions. The proteins contributing to each disease have dissimilar sequences and native structures, yet they share the commonality of forming insoluble amyloid aggregates characterized by fibrillar morphology and cross‐β structure. Presently, it is thought that the predominant agents causing cell toxicity and tissue damage are soluble, prefibrillar assemblies of these proteins. Because of the metastable nature of these prefibrillar assemblies and the noncrystalline nature of fibrillar protein aggregates, structural study of amyloid proteins is difficult. As a result, structural characterization of these proteins is typically done using combinations of low‐resolution analytical methods. Here, we present a compendium of analytical methods used to study the secondary, tertiary, and quaternary structures, and morphology of prefibrillar and fibrillar assemblies of amyloid‐forming proteins.

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Structural and Compositional Information about Pre‐Amyloid Oligomers

Zijlstra

Subramaniam

2013

Amyloid Fibrils and Prefibrillar Aggregates

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Structural characterization of β-sheeted oligomers formed on the pathway of oxidative prion protein aggregation in vitro

Cited by 51 publications

References 54 publications

Design of anti- and pro-aggregation variants to assess the effects of methionine oxidation in human prion protein

Design of anti- and pro-aggregation variants to assess the effects of methionine oxidation in human prion protein

Amyloids and Protein Aggregation—Analytical Methods

Structural and Compositional Information about Pre‐Amyloid Oligomers

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