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.
Structure of an early native-like intermediate of β2-microglobulin amyloidogenesis. / Vanderhaegen S;Fislage M;Domanska K;Versées W;Pardon E;Bellotti V;Steyaert J. - In: PROTEIN SCIENCE. - ISSN 0961-8368. - STAMPA. - 22:10(2013), pp. 1349-1357.
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Titolo: | Structure of an early native-like intermediate of β2-microglobulin amyloidogenesis. | |
Autori: | ||
Data di pubblicazione: | 2013 | |
Rivista: | ||
Citazione: | Structure of an early native-like intermediate of β2-microglobulin amyloidogenesis. / Vanderhaegen S;Fislage M;Domanska K;Versées W;Pardon E;Bellotti V;Steyaert J. - In: PROTEIN SCIENCE. - ISSN 0961-8368. - STAMPA. - 22:10(2013), pp. 1349-1357. | |
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. | |
Handle: | http://hdl.handle.net/11571/737221 | |
Appare nelle tipologie: | 1.1 Articolo in rivista |