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Monitoring the prevention of amyloid fibril formation by α‐crystallin
Author(s) -
Rekas Agata,
Jankova Lucy,
Thorn David C.,
Cappai Roberto,
Carver John A.
Publication year - 2007
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2007.06144.x
Subject(s) - fibril , thioflavin , chaperone (clinical) , crystallin , chemistry , biophysics , monomer , protein aggregation , amyloid (mycology) , peptide , biochemistry , biology , alzheimer's disease , polymer , medicine , inorganic chemistry , disease , organic chemistry , pathology
The molecular chaperone, α‐crystallin, has the ability to prevent the fibrillar aggregation of proteins implicated in human diseases, for example, amyloid β peptide and α‐synuclein. In this study, we examine, in detail, two aspects of α‐crystallin's fibril‐suppressing ability: (a) its temperature dependence, and (b) the nature of the aggregating species with which it interacts. First, the efficiency of α‐crystallin to suppress fibril formation in κ‐casein and α‐synuclein increases with temperature, despite their rate of fibrillation also increasing in the absence of α‐crystallin. This is consistent with an increased chaperone ability of α‐crystallin at higher temperatures to protect target proteins from amorphous aggregation [GB Reddy, KP Das, JM Petrash & WK Surewicz (2000) J Biol Chem 275 , 4565–4570]. Second, dual polarization interferometry was used to monitor real‐time α‐synuclein aggregation in the presence and absence of αB‐crystallin. In contrast to more common methods for monitoring the time‐dependent formation of amyloid fibrils (e.g. the binding of dyes like thioflavin T), dual polarization interferometry data did not reveal any initial lag phase, generally attributed to the formation of prefibrillar aggregates. It was shown that αB‐crystallin interrupted α‐synuclein aggregation at its earliest stages, most likely by binding to partially folded monomers and thereby preventing their aggregation into fibrillar structures.