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Structure of an early native‐like intermediate of β2‐microglobulin amyloidogenesis
Author(s) -
Vanderhaegen Saskia,
Fislage Marcus,
Domanska Katarzyna,
Versées Wim,
Pardon Els,
Bellotti Vittorio,
Steyaert Jan
Publication year - 2013
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.2321
Subject(s) - monomer , chemistry , isomerization , beta 2 microglobulin , elongation , fibril , amyloid (mycology) , crystallography , chaperone (clinical) , peptide , protein folding , biophysics , amyloid fibril , intramolecular force , stereochemistry , biochemistry , amyloid β , biology , polymer , materials science , medicine , inorganic chemistry , disease , organic chemistry , pathology , ultimate tensile strength , metallurgy , immunology , catalysis
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.