Intrinsically Disordered Protein Exhibits Both Compaction and Expansion under Macromolecular Crowding
Abstract
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.
- Authors:
- Publication Date:
- Research Org.:
- Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES); USDOE Office of Science (SC), Biological and Environmental Research (BER)
- OSTI Identifier:
- 1548612
- Alternate Identifier(s):
- OSTI ID: 1479778; OSTI ID: 1495258
- Grant/Contract Number:
- AC05-00OR22725
- Resource Type:
- Journal Article: Published Article
- Journal Name:
- Biophysical Journal
- Additional Journal Information:
- Journal Name: Biophysical Journal Journal Volume: 114 Journal Issue: 5; Journal ID: ISSN 0006-3495
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Banks, Anthony, Qin, Sanbo, Weiss, Kevin L., Stanley, Christopher B., and Zhou, Huan-Xiang. Intrinsically Disordered Protein Exhibits Both Compaction and Expansion under Macromolecular Crowding. United States: N. p., 2018.
Web. doi:10.1016/j.bpj.2018.01.011.
Banks, Anthony, Qin, Sanbo, Weiss, Kevin L., Stanley, Christopher B., & Zhou, Huan-Xiang. Intrinsically Disordered Protein Exhibits Both Compaction and Expansion under Macromolecular Crowding. United States. https://doi.org/10.1016/j.bpj.2018.01.011
Banks, Anthony, Qin, Sanbo, Weiss, Kevin L., Stanley, Christopher B., and Zhou, Huan-Xiang. 2018.
"Intrinsically Disordered Protein Exhibits Both Compaction and Expansion under Macromolecular Crowding". United States. https://doi.org/10.1016/j.bpj.2018.01.011.
@article{osti_1548612,
title = {Intrinsically Disordered Protein Exhibits Both Compaction and Expansion under Macromolecular Crowding},
author = {Banks, Anthony and Qin, Sanbo and Weiss, Kevin L. and Stanley, Christopher B. and Zhou, Huan-Xiang},
abstractNote = {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.},
doi = {10.1016/j.bpj.2018.01.011},
url = {https://www.osti.gov/biblio/1548612},
journal = {Biophysical Journal},
issn = {0006-3495},
number = 5,
volume = 114,
place = {United States},
year = {Thu Mar 01 00:00:00 EST 2018},
month = {Thu Mar 01 00:00:00 EST 2018}
}
Web of Science
Works referencing / citing this record:
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