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Comment
. 2021 Oct 12:10:e73586.
doi: 10.7554/eLife.73586.

Aggregation in the spotlight

Zihao Wang  1 , Miranda Collier  2 , Justin Benesch  1
Affiliations
Comment

Aggregation in the spotlight

Zihao Wang et al. Elife. .

Abstract

New findings clarify apparently conflicting results about how molecular agents that preserve protein integrity prevent harmful, dense aggregates from forming.

Keywords: FUS; RRM; aging; biochemistry; chaperones; chemical biology; human; molecular condensates; time-resolved quantitative XL-MS.

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Conflict of interest statement

ZW, MC, JB No competing interests declared

Figures

Figure 1.
Figure 1.. Hypothesis for a coherent mechanism of sHsp chaperone function.
Chaperones known as sHsps (colourful dots) can bind to proteins destabilised under stress conditions (‘substrates’; grey dots). They either encourage other proteins to gather with them in large protective complexes known as co-aggregates (‘aggregase’ activity; red, left); or they keep the proteins they bind apart from each other (‘holdase’ activity; blue, right) to stop these substrates from transitioning into toxic aggregates such as amyloid fibrils (grey arrows). These apparently incompatible models of chaperones’ activity can be reconciled by considering that they both aim to stop destabilised proteins from coming together in specific ways that are harmful to the cell. Sometimes, this aim is achieved by forming reversible liquid condensates requiring both aspects of sHsp function: there, the chaperones help to sequester the proteins and prevent them from becoming amyloid fibrils.
See this image and copyright information in PMC

Comment on

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