Title | Structure of an early native-like intermediate of β2-microglobulin amyloidogenesis. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Vanderhaegen, S., M. Fislage, K. Domanska, W. Versées, E. Pardon, V. Bellotti, and J. Steyaert |
Journal | Protein Sci |
Volume | 22 |
Issue | 10 |
Pagination | 1349-57 |
Date Published | 2013 Oct |
ISSN | 1469-896X |
Keywords | Amino 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. |
DOI | 10.1002/pro.2321 |
Alternate Journal | Protein Sci. |
PubMed ID | 23904325 |
PubMed Central ID | PMC3795493 |
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