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Nat Commun. 2016 Nov 30;7:13673. doi: 10.1038/ncomms13673.

Small heat shock proteins sequester misfolding proteins in near-native conformation for cellular protection and efficient refolding.

Author information

1
Center for Molecular Biology of the University of Heidelberg (ZMBH), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 282, Heidelberg D-69120, Germany.
2
German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg D-69120, Germany.
3
FOM Institute for Atomic and Molecular Physics (AMOLF), Science Park 104, Amsterdam 1098 XG, The Netherlands.

Abstract

Small heat shock proteins (sHsp) constitute an evolutionary conserved yet diverse family of chaperones acting as first line of defence against proteotoxic stress. sHsps coaggregate with misfolded proteins but the molecular basis and functional implications of these interactions, as well as potential sHsp specific differences, are poorly explored. In a comparative analysis of the two yeast sHsps, Hsp26 and Hsp42, we show in vitro that model substrates retain near-native state and are kept physically separated when complexed with either sHsp, while being completely unfolded when aggregated without sHsps. Hsp42 acts as aggregase to promote protein aggregation and specifically ensures cellular fitness during heat stress. Hsp26 in contrast lacks aggregase function but is superior in facilitating Hsp70/Hsp100-dependent post-stress refolding. Our findings indicate the sHsps of a cell functionally diversify in stress defence, but share the working principle to promote sequestration of misfolding proteins for storage in native-like conformation.

PMID:
27901028
PMCID:
PMC5141385
DOI:
10.1038/ncomms13673
[Indexed for MEDLINE]
Free PMC Article

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