Crowder-directed interactions and conformational dynamics in multistimuli-responsive intrinsically disordered protein

The consequences of crowding on the dynamic conformational ensembles of intrinsically disordered proteins (IDPs) remain unresolved because of their ultrafast motion. Here, we report crowder-induced interactions and conformational dynamics of a prototypical multistimuli-responsive IDP, Rec1-resilin....

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Published in:Science advances 2022-12, Vol.8 (51), p.eabq2202-eabq2202
Main Authors: Balu, Rajkamal, Wanasingha, Nisal, Mata, Jitendra P, Rekas, Agata, Barrett, Susan, Dumsday, Geoff, Thornton, Aaron W, Hill, Anita J, Roy Choudhury, Namita, Dutta, Naba K
Format: Article
Language:English
Subjects:
Biophysics
Intrinsically Disordered Proteins - chemistry
Macromolecular Substances
Physical and Materials Sciences
Protein Conformation
SciAdv r-articles
Structural Biology
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Summary:The consequences of crowding on the dynamic conformational ensembles of intrinsically disordered proteins (IDPs) remain unresolved because of their ultrafast motion. Here, we report crowder-induced interactions and conformational dynamics of a prototypical multistimuli-responsive IDP, Rec1-resilin. The effects of a range of crowders of varying sizes, forms, topologies, and concentrations were examined using spectroscopic, spectrofluorimetric, and contrast-matching small- and ultrasmall-angle neutron scattering investigation. To achieve sufficient neutron contrast against the crowders, deuterium-labeled Rec1-resilin was biosynthesized successfully. Moreover, the ab initio "shape reconstruction" approach was used to obtain three-dimensional models of the conformational assemblies. The IDP revealed crowder-specific systematic extension and compaction with the level of macromolecular crowding. Last, a robust extension-contraction model has been postulated to capture the fundamental phenomena governing the observed behavior of IDPs. The study provides insights and fresh perspectives for understanding the interactions and structural dynamics of IDPs in crowded states.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.abq2202