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Title: 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}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record at https://doi.org/10.1016/j.bpj.2018.01.011

Citation Metrics:
Cited by: 44 works
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Works referencing / citing this record:

Features of molecular recognition of intrinsically disordered proteins via coupled folding and binding
journal, September 2019


Commonly used FRET fluorophores promote collapse of an otherwise disordered protein
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Generation of the configurational ensemble of an intrinsically disordered protein from unbiased molecular dynamics simulation
journal, September 2019