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Structure of an early native-like intermediate of ?2-microglobulin amyloidogenesis.

ABSTRACT: To investigate early intermediates of ?2-microglobulin (?2m) amyloidogenesis, we solved the structure of ?2m 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 ?2m monomer under physiological conditions. The complex of P32G ?2m 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 ?2m amyloid formation.

SUBMITTER: Vanderhaegen S

PROVIDER: S-EPMC3795493 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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

Vanderhaegen Saskia S Fislage Marcus M Domanska Katarzyna K Versées Wim W Pardon Els E Bellotti Vittorio V Steyaert Jan J

Protein science : a publication of the Protein Society 20130820 10

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 ...[more]

PMID: 23904325

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