Characteristics of Human Lysozyme and Its Disease‐Related Mutants in their Unfolded States

Sziegat, Friederike; Wirmer‐Bartoschek, Julia; Schwalbe, Harald

doi:10.1002/ange.201008040

Cited by 5 publications

(2 citation statements)

References 38 publications

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“…70 % and identity of ca. 60 %, [16] the obtained fibrils show different architectures compared to HEWL (Figure 2A,B).…”

Section: Resultsmentioning

confidence: 97%

“…In particular, cryo‐EM is scarcely used for analysis of fibrils formed in vitro in denaturing conditions. We demonstrate that relatively small differences in amino acid sequence [16] indeed translate into essentially different fibril structures at deeper levels of organization, i. e., the secondary structure and protofibril structure/handedness. Importantly, we have shown for the first time, that agitation not only significantly affects the fibril morphology, [3b,5a] but can reverse the protofilament handedness.…”

Section: Introductionmentioning

confidence: 86%

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Chiral and Structural Polymorphism of Fibril Architectures of Homologous Lysozymes

Hachlica

Rawski

Górecki

et al. 2023

Chemistry A European J

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Amyloid fibrils are fascinating and complex structures with the multilayered chiral organization. Using the multimodal methodology, including VCD, ECD, cryo‐EM, and TEM, we characterized in detail different levels of organization (secondary structure/protofilament/mesoscopic structure) of amyloid fibrils prepared from proteins highly homologous in the structure (hen egg white and human lysozymes). Our results demonstrate that small changes in the native protein structure or preparation conditions translate into significant differences in the handedness and architecture of the formed fibrils at various levels of their complexity. In particular, fibrils of hen egg white and human lysozymes obtained in vitro at the same preparation conditions, possess different secondary structure, protofilament twist and ultrastructure. Yet, formed fibrils adopted a relatively similar mesoscopic structure, as observed in high‐resolution 3D cryo‐EM, scarcely used up to now for fibrils obtained in vitro in denaturing condition. Our results add to other puzzling experiments implicating the indeterministic nature of fibril formation.

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“…70 % and identity of ca. 60 %, [16] the obtained fibrils show different architectures compared to HEWL (Figure 2A,B).…”

Section: Resultsmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 86%

Chiral and Structural Polymorphism of Fibril Architectures of Homologous Lysozymes

Hachlica

Rawski

Górecki

et al. 2023

Chemistry A European J

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Steuerung der α‐Synuclein‐Aggregation durch Bindung einer β‐Haarnadel

et al. 2014

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Fehlfaltung, Aggregation und Amyloidfibrillenbildung des Proteins a-Synuclein (a-syn) sind an der Pathogenese der Parkinson-Krankheit und weiterer Synucleinopathien beteiligt. Die Entwicklung der Amyloid-Toxizität steht in Zusammenhang mit der Bildung partiell gefalteter Aggregationsintermediate. Hier beschreiben wir die Entwicklung einer Klasse gegen a-syn gerichteter Bindeproteine, die wir als b-Wrapine (b-Wrap-Proteine) bezeichnen. Die NMR-Struktur eines a-syn:b-Wrapin-Komplexes zeigt eine b-Haarnadel-Konformation von a-syn im Sequenzbereich a-syn(37-54). Substçchiometrische Mengen des Bindeproteins inhibieren die a-syn-Aggregation und -Toxizität, das b-Wrapin greift folglich in die Bildung der Aggregationskeime ein. Angewandte Chemie 4313

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Sequestration of a β‐Hairpin for Control of α‐Synuclein Aggregation

et al. 2014

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The misfolding and aggregation of the protein α-synuclein (α-syn), which results in the formation of amyloid fibrils, is involved in the pathogenesis of Parkinson's disease and other synucleinopathies. The emergence of amyloid toxicity is associated with the formation of partially folded aggregation intermediates. Here, we engineered a class of binding proteins termed β-wrapins (β-wrap proteins) with affinity for α-synuclein (α-syn). The NMR structure of an α-syn:β-wrapin complex reveals a β-hairpin of α-syn comprising the sequence region α-syn(37-54). The β-wrapin inhibits α-syn aggregation and toxicity at substoichiometric concentrations, demonstrating that it interferes with the nucleation of aggregation.

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Characteristics of Human Lysozyme and Its Disease‐Related Mutants in their Unfolded States

Cited by 5 publications

References 38 publications

Chiral and Structural Polymorphism of Fibril Architectures of Homologous Lysozymes

Chiral and Structural Polymorphism of Fibril Architectures of Homologous Lysozymes

Steuerung der α‐Synuclein‐Aggregation durch Bindung einer β‐Haarnadel

Sequestration of a β‐Hairpin for Control of α‐Synuclein Aggregation

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