Imperial College London
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Dr Francesco A. Aprile

Faculty of Natural Sciences, Department of Chemistry

Lecturer in Chemistry
 
 
 
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Contact

 

+44 (0)20 7594 5545f.aprile Website

 
 
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Location

 

110FMolecular Sciences Research HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Scheidt:2021:10.1073/pnas.2108790118|1of8,
author = {Scheidt, T and Carozza, JA and Kolbe, CC and Aprile, FA and Tkachenko, O and Bellaiche, MMJ and Meisl, G and Peter, QAE and Herling, TW and Ness, S and Castellana-Cruz, M and Benesch, JLP and Vendruscolo, M and Dobson, CM and Arosio, P and Knowles, TPJ},
doi = {10.1073/pnas.2108790118|1of8},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
pages = {1--8},
title = {The binding of the small heat-shock protein alpha B-crystallin to fibrils of alpha-synuclein is driven by entropic forces},
url = {http://dx.doi.org/10.1073/pnas.2108790118|1of8},
volume = {118},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Molecular chaperones are key components of the cellular proteostasis network whose role includes the suppression of the formation and proliferation of pathogenic aggregates associated with neurodegenerative diseases. The molecular principles that allow chaperones to recognize misfolded and aggregated proteins remain, however, incompletely understood. To address this challenge, here we probe the thermodynamics and kinetics of the interactions between chaperones and protein aggregates under native solution conditions using a microfluidic platform. We focus on the binding between amyloid fibrils of α-synuclein, associated with Parkinson’s disease, to the small heat-shock protein αB-crystallin, a chaperone widely involved in the cellular stress response. We find that αB-crystallin binds to α-synuclein fibrils with high nanomolar affinity and that the binding is driven by entropy rather than enthalpy. Measurements of the change in heat capacity indicate significant entropic gain originates from the disassembly of the oligomeric chaperones that function as an entropic buffer system. These results shed light on the functional roles of chaperone oligomerization and show that chaperones are stored as inactive complexes which are capable of releasing active subunits to target aberrant misfolded species.
AU  - Scheidt,T
AU  - Carozza,JA
AU  - Kolbe,CC
AU  - Aprile,FA
AU  - Tkachenko,O
AU  - Bellaiche,MMJ
AU  - Meisl,G
AU  - Peter,QAE
AU  - Herling,TW
AU  - Ness,S
AU  - Castellana-Cruz,M
AU  - Benesch,JLP
AU  - Vendruscolo,M
AU  - Dobson,CM
AU  - Arosio,P
AU  - Knowles,TPJ
DO  - 10.1073/pnas.2108790118|1of8
EP  - 8
PY  - 2021///
SN  - 0027-8424
SP  - 1
TI  - The binding of the small heat-shock protein alpha B-crystallin to fibrils of alpha-synuclein is driven by entropic forces
T2  - Proceedings of the National Academy of Sciences of the United States of America
UR  - http://dx.doi.org/10.1073/pnas.2108790118|1of8
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000704002000014&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.pnas.org/content/118/38/e2108790118
UR  - http://hdl.handle.net/10044/1/92310
VL  - 118
ER  -
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