Intrinsically Disordered Protein Exhibits Both Compaction and Expansion under Macromolecular Crowding
Conformational malleability allows intrinsically disordered proteins (IDPs) to respond agilely to their environments, such as nonspecifically interacting with in vivo bystander macromolecules (or crowders). Previous studies have emphasized conformational compaction of IDPs due to steric repulsion by macromolecular crowders, but effects of soft attraction are largely unexplored. Here we studied the conformational ensembles of the IDP FlgM in both polymer and protein crowders by small-angle neutron scattering. As crowder concentrations increased, the mean radius of gyration of FlgM first decreased but then exhibited an uptick. Ensemble optimization modeling indicated that FlgM conformations under protein crowding segregated into two distinct populations, one compacted and one extended. Coarse-grained simulations showed that compacted conformers fit into an interstitial void and occasionally bind to a surrounding crowder, whereas extended conformers snake through interstitial crevices and bind multiple crowders simultaneously. In conclusion, crowder-induced conformational segregation may facilitate various cellular functions of IDPs.
- Research Organization:
- Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC), Basic Energy Sciences (BES); USDOE Office of Science (SC), Biological and Environmental Research (BER)
- Grant/Contract Number:
- AC05-00OR22725
- OSTI ID:
- 1548612
- Alternate ID(s):
- OSTI ID: 1479778; OSTI ID: 1495258
- Journal Information:
- Biophysical Journal, Journal Name: Biophysical Journal Vol. 114 Journal Issue: 5; ISSN 0006-3495
- Publisher:
- ElsevierCopyright Statement
- Country of Publication:
- United States
- Language:
- English
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