eprintid: 10076232
rev_number: 19
eprint_status: archive
userid: 608
dir: disk0/10/07/62/32
datestamp: 2019-06-19 14:06:19
lastmod: 2021-10-04 01:02:09
status_changed: 2019-06-19 14:06:19
type: article
metadata_visibility: show
creators_name: Peran, I
creators_name: Holehouse, AS
creators_name: Carrico, IS
creators_name: Pappu, RV
creators_name: Bilsel, O
creators_name: Raleigh, DP
title: Unfolded states under folding conditions accommodate sequence-specific conformational preferences with random coil-like dimensions
ispublished: pub
divisions: UCL
divisions: B02
divisions: C08
divisions: D09
divisions: G03
keywords: FRET, compaction transition, protein folding, unfolded state
note: © 2019 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/).
abstract: Proteins are marginally stable molecules that fluctuate between folded and unfolded states. Here, we provide a high-resolution description of unfolded states under refolding conditions for the N-terminal domain of the L9 protein (NTL9). We use a combination of time-resolved Förster resonance energy transfer (FRET) based on multiple pairs of minimally perturbing labels, time-resolved small-angle X-ray scattering (SAXS), all-atom simulations, and polymer theory. Upon dilution from high denaturant, the unfolded state undergoes rapid contraction. Although this contraction occurs before the folding transition, the unfolded state remains considerably more expanded than the folded state and accommodates a range of local and nonlocal contacts, including secondary structures and native and nonnative interactions. Paradoxically, despite discernible sequence-specific conformational preferences, the ensemble-averaged properties of unfolded states are consistent with those of canonical random coils, namely polymers in indifferent (theta) solvents. These findings are concordant with theoretical predictions based on coarse-grained models and inferences drawn from single-molecule experiments regarding the sequence-specific scaling behavior of unfolded proteins under folding conditions.
date: 2019-06-18
date_type: published
official_url: https://doi.org/10.1073/pnas.1818206116
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
article_type_text: Journal Article
verified: verified_manual
elements_id: 1664446
doi: 10.1073/pnas.1818206116
pii: 1818206116
language_elements: English
lyricists_name: Raleigh, Daniel
lyricists_id: DRALE20
actors_name: Flynn, Bernadette
actors_id: BFFLY94
actors_role: owner
full_text_status: public
publication: Proceedings of the National Academy of Sciences of the United States of America
volume: 116
number: 25
pagerange: 12301-12310
event_location: United States
issn: 1091-6490
citation:        Peran, I;    Holehouse, AS;    Carrico, IS;    Pappu, RV;    Bilsel, O;    Raleigh, DP;      (2019)    Unfolded states under folding conditions accommodate sequence-specific conformational preferences with random coil-like dimensions.                   Proceedings of the National Academy of Sciences of the United States of America , 116  (25)   pp. 12301-12310.    10.1073/pnas.1818206116 <https://doi.org/10.1073/pnas.1818206116>.       Green open access   
 
document_url: https://discovery-pp.ucl.ac.uk/id/eprint/10076232/8/Raleigh_Unfolded%20states%20under%20folding%20conditions%20accommodate%20sequence-specific%20conformational%20preferences%20with%20random%20coil-like%20dimensions_VoR.pdf