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@ARTICLE{Trner:909069,
author = {Törner, Ricarda and Kupreichyk, Tatsiana and Gremer,
Lothar and Debled, Elisa Colas and Fenel, Daphna and
Schemmert, Sarah and Gans, Pierre and Willbold, Dieter and
Schoehn, Guy and Hoyer, Wolfgang and Boisbouvier, Jerome},
title = {{S}tructural basis for the inhibition of {IAPP} fibril
formation by the co-chaperonin prefoldin.},
journal = {Nature Communications},
volume = {13},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {FZJ-2022-02987},
pages = {2363},
year = {2022},
abstract = {Chaperones, as modulators of protein conformational states,
are key cellular actors to prevent the accumulation of
fibrillar aggregates. Here, we integrated kinetic
investigations with structural studies to elucidate how the
ubiquitous co-chaperonin prefoldin inhibits diabetes
associated islet amyloid polypeptide (IAPP) fibril
formation. We demonstrated that both human and archaeal
prefoldin interfere similarly with the IAPP fibril
elongation and secondary nucleation pathways. Using archaeal
prefoldin model, we combined nuclear magnetic resonance
spectroscopy with electron microscopy to establish that the
inhibition of fibril formation is mediated by the binding of
prefoldin's coiled-coil helices to the flexible IAPP
N-terminal segment accessible on the fibril surface and
fibril ends. Atomic force microscopy demonstrates that
binding of prefoldin to IAPP leads to the formation of lower
amounts of aggregates, composed of shorter fibrils,
clustered together. Linking structural models with observed
fibrillation inhibition processes opens perspectives for
understanding the interference between natural chaperones
and formation of disease-associated amyloids.},
keywords = {Amyloid: metabolism / Chaperonins / Humans / Islet Amyloid
Polypeptide / Molecular Chaperones: metabolism / Amyloid
(NLM Chemicals) / Islet Amyloid Polypeptide (NLM Chemicals)
/ Molecular Chaperones (NLM Chemicals) / prefoldin (NLM
Chemicals) / Chaperonins (NLM Chemicals)},
cin = {IBI-7},
ddc = {500},
cid = {I:(DE-Juel1)IBI-7-20200312},
pnm = {5244 - Information Processing in Neuronal Networks
(POF4-524) / BETACONTROL - Control of amyloid formation via
beta-hairpin molecular recognition features (726368)},
pid = {G:(DE-HGF)POF4-5244 / G:(EU-Grant)726368},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35501361},
pmc = {pmc:PMC9061850},
UT = {WOS:000789924700014},
doi = {10.1038/s41467-022-30042-y},
url = {https://juser.fz-juelich.de/record/909069},
}