The Anti-Aggregation Holdase Hsp33 Promotes the Formation of Folded Protein Structures
Autor: | Sergey Bezrukavnikov, Kingshuk Ghosh, Fatemeh Moayed, Bastian Groitl, Sander J. Tans, Claudia M. Cremers, Guenter Kramer, Ursula Jakob, Mohsin M. Naqvi |
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Rok vydání: | 2019 |
Předmět: |
Models
Molecular 0303 health sciences Protein Folding biology Chemistry Anti aggregation Biophysics Articles 03 medical and health sciences Maltose-binding protein Protein Aggregates 0302 clinical medicine Protein structure Chaperone (protein) Hsp33 biology.protein 030217 neurology & neurosurgery Heat-Shock Proteins 030304 developmental biology |
Zdroj: | Biophys J |
ISSN: | 1542-0086 |
Popis: | Holdase chaperones are known to be central to suppressing aggregation, but how they affect substrate conformations remains poorly understood. Here, we use optical tweezers to study how the holdase Hsp33 alters folding transitions within single maltose binding proteins and aggregation transitions between maltose binding protein substrates. Surprisingly, we find that Hsp33 not only suppresses aggregation but also guides the folding process. Two modes of action underlie these effects. First, Hsp33 binds unfolded chains, which suppresses aggregation between substrates and folding transitions within substrates. Second, Hsp33 binding promotes substrate states in which most of the chain is folded and modifies their structure, possibly by intercalating its intrinsically disordered regions. A statistical ensemble model shows how Hsp33 function results from the competition between these two contrasting effects. Our findings reveal an unexpectedly comprehensive functional repertoire for Hsp33 that may be more prevalent among holdases and dispels the notion of a strict chaperone hierarchy. |
Databáze: | OpenAIRE |
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