Structure of an early native-like intermediate of β2-microglobulin amyloidogenesis.

TitleStructure of an early native-like intermediate of β2-microglobulin amyloidogenesis.
Publication TypeJournal Article
Year of Publication2013
AuthorsVanderhaegen, S., M. Fislage, K. Domanska, W. Versées, E. Pardon, V. Bellotti, and J. Steyaert
JournalProtein Sci
Date Published2013 Oct
KeywordsAmino Acid Motifs, beta 2-Microglobulin, Circular Dichroism, Crystallography, X-Ray, Escherichia coli, Glycine, Humans, Models, Molecular, Mutation, Missense, Proline, Protein Folding, Protein Structure, Tertiary, Single-Domain Antibodies

To investigate early intermediates of β2-microglobulin (β2m) amyloidogenesis, we solved the structure of β2m containing the amyloidogenic Pro32Gly mutation by X-ray crystallography. One nanobody (Nb24) that efficiently blocks fibril elongation was used as a chaperone to co-crystallize the Pro32Gly β2m monomer under physiological conditions. The complex of P32G β2m with Nb24 reveals a trans peptide bond at position 32 of this amyloidogenic variant, whereas Pro32 adopts the cis conformation in the wild-type monomer, indicating that the cis to trans isomerization at Pro32 plays a critical role in the early onset of β2m amyloid formation.

Alternate JournalProtein Sci.
PubMed ID23904325
PubMed Central IDPMC3795493
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