Local versus global fold switching in protein evolution: insight from a three-letter continuous model.
(2015) In Physical Biology 12(2).- Abstract
- Recent design experiments have demonstrated that some proteins can switch their folds in response to a small number of point mutations either directly, in a single mutational step, or via intermediate bistable sequences, which populate two different folds simultaneously. Here we explore the hypothesis that bistable intermediates are more common in switches between structurally similar folds while direct switches are more common between dissimilar folds. To this end, we use a reduced model with seven atoms per amino acid and three amino acid types as a biophysical basis for protein folding and stability. We compare a set of mutational pathways, selected for optimal stability properties, that lead to switches between β-hairpin and α-helix... (More)
- Recent design experiments have demonstrated that some proteins can switch their folds in response to a small number of point mutations either directly, in a single mutational step, or via intermediate bistable sequences, which populate two different folds simultaneously. Here we explore the hypothesis that bistable intermediates are more common in switches between structurally similar folds while direct switches are more common between dissimilar folds. To this end, we use a reduced model with seven atoms per amino acid and three amino acid types as a biophysical basis for protein folding and stability. We compare a set of mutational pathways, selected for optimal stability properties, that lead to switches between β-hairpin and α-helix folds with 16 amino acids and between [Formula: see text] and [Formula: see text] folds with 35 amino acids, respectively. Fold switching in each case is sharp, taking only a few mutations to be completed. While the sharpness of mutationally driven protein fold switching can be traced to a shift in the energy balance of the two native states, conformational entropy contributes to determining the point at which fold switching occurs along a pathway. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/5143001
- author
- Holzgräfe, Christian LU and Wallin, Stefan LU
- organization
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Physical Biology
- volume
- 12
- issue
- 2
- article number
- 026002
- publisher
- IOP Publishing
- external identifiers
-
- pmid:25706822
- wos:000357203400005
- scopus:84928798137
- pmid:25706822
- ISSN
- 1478-3975
- DOI
- 10.1088/1478-3975/12/2/026002
- language
- English
- LU publication?
- yes
- id
- 5d21c742-596a-48fc-ac4e-3f36b65a5eff (old id 5143001)
- date added to LUP
- 2016-04-01 10:53:01
- date last changed
- 2024-01-07 03:36:03
@article{5d21c742-596a-48fc-ac4e-3f36b65a5eff,
abstract = {{Recent design experiments have demonstrated that some proteins can switch their folds in response to a small number of point mutations either directly, in a single mutational step, or via intermediate bistable sequences, which populate two different folds simultaneously. Here we explore the hypothesis that bistable intermediates are more common in switches between structurally similar folds while direct switches are more common between dissimilar folds. To this end, we use a reduced model with seven atoms per amino acid and three amino acid types as a biophysical basis for protein folding and stability. We compare a set of mutational pathways, selected for optimal stability properties, that lead to switches between β-hairpin and α-helix folds with 16 amino acids and between [Formula: see text] and [Formula: see text] folds with 35 amino acids, respectively. Fold switching in each case is sharp, taking only a few mutations to be completed. While the sharpness of mutationally driven protein fold switching can be traced to a shift in the energy balance of the two native states, conformational entropy contributes to determining the point at which fold switching occurs along a pathway.}},
author = {{Holzgräfe, Christian and Wallin, Stefan}},
issn = {{1478-3975}},
language = {{eng}},
number = {{2}},
publisher = {{IOP Publishing}},
series = {{Physical Biology}},
title = {{Local versus global fold switching in protein evolution: insight from a three-letter continuous model.}},
url = {{http://dx.doi.org/10.1088/1478-3975/12/2/026002}},
doi = {{10.1088/1478-3975/12/2/026002}},
volume = {{12}},
year = {{2015}},
}