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
Volume22
Issue10
Pagination1349-57
Date Published2013 Oct
ISSN1469-896X
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
Abstract

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.

DOI10.1002/pro.2321
Alternate JournalProtein Sci.
PubMed ID23904325
PubMed Central IDPMC3795493
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