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Coupled Folding-Binding in a Hydrophobic/Polar Protein Model: Impact of Synergistic Folding and Disordered Flanks

Bhattacherjee, Arnab LU and Wallin, Stefan LU (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)
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author
organization
publishing date
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
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
2012-02-24 08:18:38
date last changed
2017-10-01 03:22:42
@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},
  keyword      = {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          = {http://dx.doi.org/10.1016/j.bpj.2011.12.008},
  volume       = {102},
  year         = {2012},
}