Coupled Folding-Binding in a Hydrophobic/Polar Protein Model: Impact of Synergistic Folding and Disordered Flanks
(2012) In Biophysical Journal 102(3). p.569-578- Abstract
- Coupled folding-binding is central to the function of many intrinsically disordered proteins, yet not fully understood. With a continuous three-letter protein model, we explore the free-energy landscape of pairs of interacting sequences and how it is impacted by 1), variations in the binding mechanism; and 2), the addition of disordered flanks to the binding region. In particular, we focus on two sequences, one with 16 and one with 35 amino acids, which make a stable dimeric three-helix bundle at low temperatures. Three distinct binding mechanisms are realized by altering the stabilities of the individual monomers: docking, coupled folding-binding of a single α-helix, and synergistic folding and binding. Compared to docking, the... (More)
- Coupled folding-binding is central to the function of many intrinsically disordered proteins, yet not fully understood. With a continuous three-letter protein model, we explore the free-energy landscape of pairs of interacting sequences and how it is impacted by 1), variations in the binding mechanism; and 2), the addition of disordered flanks to the binding region. In particular, we focus on two sequences, one with 16 and one with 35 amino acids, which make a stable dimeric three-helix bundle at low temperatures. Three distinct binding mechanisms are realized by altering the stabilities of the individual monomers: docking, coupled folding-binding of a single α-helix, and synergistic folding and binding. Compared to docking, the free-energy barrier for binding is reduced when the single α-helix is allowed to fold upon binding, but only marginally. A greater reduction is found for synergistic folding, which in addition results in a binding transition state characterized by very few interchain contacts. Disordered flanking chain segments attached to the α-helix sequence can, despite a negligible impact on the dimer stability, lead to a downhill free-energy surface in which the barrier for binding is eliminated. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2364100
- author
- Bhattacherjee, Arnab LU and Wallin, Stefan LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- protein folding, protein-protein interaction, coupled folding-binding, Monte Carlo simulation
- in
- Biophysical Journal
- volume
- 102
- issue
- 3
- pages
- 569 - 578
- publisher
- Cell Press
- external identifiers
-
- wos:000300122500023
- scopus:84856694618
- pmid:22325280
- ISSN
- 1542-0086
- DOI
- 10.1016/j.bpj.2011.12.008
- language
- English
- LU publication?
- yes
- id
- 078decf6-fc3b-4aff-adcb-1a95b2e93e98 (old id 2364100)
- date added to LUP
- 2016-04-01 10:45:35
- date last changed
- 2024-04-21 20:13:44
@article{078decf6-fc3b-4aff-adcb-1a95b2e93e98,
abstract = {{Coupled folding-binding is central to the function of many intrinsically disordered proteins, yet not fully understood. With a continuous three-letter protein model, we explore the free-energy landscape of pairs of interacting sequences and how it is impacted by 1), variations in the binding mechanism; and 2), the addition of disordered flanks to the binding region. In particular, we focus on two sequences, one with 16 and one with 35 amino acids, which make a stable dimeric three-helix bundle at low temperatures. Three distinct binding mechanisms are realized by altering the stabilities of the individual monomers: docking, coupled folding-binding of a single α-helix, and synergistic folding and binding. Compared to docking, the free-energy barrier for binding is reduced when the single α-helix is allowed to fold upon binding, but only marginally. A greater reduction is found for synergistic folding, which in addition results in a binding transition state characterized by very few interchain contacts. Disordered flanking chain segments attached to the α-helix sequence can, despite a negligible impact on the dimer stability, lead to a downhill free-energy surface in which the barrier for binding is eliminated.}},
author = {{Bhattacherjee, Arnab and Wallin, Stefan}},
issn = {{1542-0086}},
keywords = {{protein folding; protein-protein interaction; coupled folding-binding; Monte Carlo simulation}},
language = {{eng}},
number = {{3}},
pages = {{569--578}},
publisher = {{Cell Press}},
series = {{Biophysical Journal}},
title = {{Coupled Folding-Binding in a Hydrophobic/Polar Protein Model: Impact of Synergistic Folding and Disordered Flanks}},
url = {{https://lup.lub.lu.se/search/files/2110715/2970545.pdf}},
doi = {{10.1016/j.bpj.2011.12.008}},
volume = {{102}},
year = {{2012}},
}