TY  - JOUR
AU  - Larsson, Johan N. K.
AU  - Kumar, Ranjeet
AU  - Buratti, Fiamma Ayelen
AU  - Nyström, Sofie
AU  - Wittung-Stafshede, Pernilla
AU  - Hammarstrom, Per
TI  - Heat shock protein 10 as a chaperone modulating α‐synuclein amyloid fibril formation
JO  - Protein science
VL  - 35
IS  - 2
SN  - 0961-8368
CY  - Hoboken, NJ
PB  - Wiley
M1  - PUBDB-2026-00754
SP  - e70452
PY  - 2026
AB  - HSP10 is a well-known human co-chaperone that interacts with HSP60 to comprise the HSP60/10 chaperonin complex which upholds mitochondrial proteostasis. HSP10 also demonstrates independent roles in binding to misfolded proteins and interacts with several amyloidogenic client proteins. Using a variety of biophysical and biochemical methods, we studied the interactions of HSP10 with the amyloidogenic protein α-synuclein (α-syn) associated with Parkinson's disease. HSP10 efficiently inhibited fibril formation of wild type (WT) and disease-mutant A30P α-syn at sufficient concentrations of chaperone by both binding to α-syn monomers and by blocking secondary nucleation on fibril surfaces. However, under sub-stoichiometric conditions, below 1:5 (HSP10:α-syn), the chaperone sequestered multiple A30P α-syn monomers and thereby promoted nucleation of fibril formation with a magnitude comparable to the efficacy of seeding with preformed fibrils. The fibril formation acceleration effect of the HSP10 chaperone was client-specific as it was observed for A30P but not WT α-syn. Our results broaden the scope of HSP10 chaperone activity and can have implications for disease onset in synucleinopathies.
LB  - PUB:(DE-HGF)16
DO  - DOI:10.1002/pro.70452
UR  - https://bib-pubdb1.desy.de/record/646209
ER  -