Two Bacterial Small Heat Shock Proteins, IbpA and IbpB, Form a Functional Heterodimer

JOURNAL OF MOLECULAR BIOLOGY

卷:433

Article

Pirog, Artur¹  Cantini, Francesca^2,3  Nierzwicki, Lukasz⁴  Obuchowski, Igor¹  Tomiczek, Bartlomiej¹  Czub, Jacek⁴  Liberek, Krzysztof¹ 

[1] Univ Gdansk, Intercoll Fac Biotechnol UG MUG, Abrahama 58, PL-80307 Gdansk, Poland

[2] Univ Florence, Magnet Resonance Ctr, Via L Sacconi 6, I-50019 Sesto Fiorentino, Italy

[3] Univ Florence, Dept Chem, Via L Sacconi 6, I-50019 Sesto Fiorentino, Italy

[4] Gdansk Univ Technol, Dept Phys Chem, Narutowicza 11-12, PL-80233 Gdansk, Poland

关键词: bacterial small heat shock proteins;    chaperones;    modification of protein aggregation;    protein refolding;    heterodimer of sHsps;   

DOI  :  10.1016/j.jmb.2021.167054

来源: Elsevier

【 摘 要 】

Small heat shock proteins (sHsps) are a conserved class of ATP-independent chaperones which in stress conditions bind to unfolded protein substrates and prevent their irreversible aggregation. Substrates trapped in sHsps-containing aggregates are efficiently refolded into native structures by ATP-dependent Hsp70 and Hsp100 chaperones. Most gamma-proteobacteria possess a single sHsp (IbpA), while in a subset of Enterobacterales, as a consequence of ibpA gene duplication event, a two-protein sHsp (IbpA and IbpB) system has evolved. IbpA and IbpB are functionally divergent. Purified IbpA, but not IbpB, stably interacts with aggregated substrates, yet both sHsps are required to be present at the substrate denaturation step for subsequent efficient Hsp70-Hsp100-dependent substrate refolding. IbpA and IbpB interact with each other, influence each other's expression levels and degradation rates. However, the crucial information on how these two sHsps interact and what is the basic building block required for proper sHsps functioning was missing. Here, based on NMR, mass spectrometry and crosslinking studies, we show that IbpA-IbpB heterodimer is a dominating functional unit of the two sHsp system in Enterobacterales. The principle of heterodimer formation is similar to one described for homodimers of single bacterial sHsps. beta-hairpins formed by strands beta 5 and beta 7 of IbpA or IbpB crystallin domains associate with the other one's beta-sandwich in the heterodimer structure. Relying on crosslinking and molecular dynamics studies, we also propose the orientation of two IbpA-IbpB heterodimers in a higher order tetrameric structure. (C) 2021 The Author(s). Published by Elsevier Ltd.

【 授权许可】

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