Regulation of small heat-shock proteins by hetero-oligomer formation

Evgeny V. Mymrikov, Mareike Riedl, Carsten Peters, Sevil Weinkauf, Martin Haslbeck, Johannes Buchner

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

29 Zitate (Scopus)

Abstract

Small heat-shock proteins (sHsps) compose the most widespread family of molecular chaperones. The human genome encodes 10 different sHsps (HspB1-10). It has been shown that HspB1 (Hsp27), HspB5 (αB-crystallin), and HspB6 (Hsp20) can form hetero-oligomers in vivo. However, the impact of hetero-oligomerization on their structure and chaperone mechanism remains enigmatic. Here, we analyzed hetero-oligomer formation in human cells and in vitro using purified proteins. Our results show that the effect of hetero-oligomer formation on the composition of the sHsp ensembles and their chaperone activities depends strongly on the respective sHsps involved. We observed that hetero-oligomer formation between HspB1 and HspB5 leads to an ensemble that is dominated by species larger than the individual homo-oligomers. In contrast, the interaction of dimeric HspB6 with either HspB1 or HspB5 oligomers shifted the ensemble toward smaller oligomers. We noted that the larger HspB1-HspB5 hetero-oligomers are less active and that HspB6 activates HspB5 by dissociation to smaller oligomer complexes. The chaperone activity of HspB1-HspB6 hetero-oligomers, however, was modulated in a substrate-specific manner, presumably due to the specific enrichment of an HspB1-HspB6 heterodimer. These heterodimeric species may allow the tuning of the chaperone properties toward specific substrates. We conclude that sHsp hetero-oligomerization exerts distinct regulatory effects depending on the sHsps involved.

OriginalspracheEnglisch
Seiten (von - bis)158-169
Seitenumfang12
FachzeitschriftJournal of Biological Chemistry
Jahrgang295
Ausgabenummer1
DOIs
PublikationsstatusVeröffentlicht - 3 Jan. 2020

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