The effect of multisite phosphorylation on the conformational properties of intrinsically disordered proteins
(2021) In International Journal of Molecular Sciences 22(20).- Abstract
Intrinsically disordered proteins are involved in many biological processes such as signaling, regulation, and recognition. A common strategy to regulate their function is through phosphorylation, as it can induce changes in conformation, dynamics, and interactions with binding partners. Although phosphorylated intrinsically disordered proteins have received increased attention in recent years, a full understanding of the conformational and structural implications of phosphorylation has not yet been achieved. Here, we present all-atom molecular dynamics simulations of five disordered peptides originated from tau, statherin, and β-casein, in both phosphorylated and non-phosphorylated state, to compare changes in global dimensions and... (More)
Intrinsically disordered proteins are involved in many biological processes such as signaling, regulation, and recognition. A common strategy to regulate their function is through phosphorylation, as it can induce changes in conformation, dynamics, and interactions with binding partners. Although phosphorylated intrinsically disordered proteins have received increased attention in recent years, a full understanding of the conformational and structural implications of phosphorylation has not yet been achieved. Here, we present all-atom molecular dynamics simulations of five disordered peptides originated from tau, statherin, and β-casein, in both phosphorylated and non-phosphorylated state, to compare changes in global dimensions and structural elements, in an attempt to gain more insight into the controlling factors. The changes are in qualitative agreement with experimental data, and we observe that the net charge is not enough to predict the impact of phosphorylation on the global dimensions. Instead, the distribution of phosphorylated and positively charged residues throughout the sequence has great impact due to the formation of salt bridges. In statherin, a preference for arginine–phosphoserine interaction over arginine–tyrosine accounts for a global expansion, despite a local contraction of the phosphorylated region, which implies that also non-charged residues can influence the effect of phosphorylation.
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- author
- Rieloff, Ellen LU and Skepö, Marie LU
- organization
- publishing date
- 2021-10-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Force fields, Intrinsically disordered proteins, Phosphorylation
- in
- International Journal of Molecular Sciences
- volume
- 22
- issue
- 20
- article number
- 11058
- publisher
- MDPI AG
- external identifiers
-
- scopus:85117029646
- pmid:34681718
- ISSN
- 1661-6596
- DOI
- 10.3390/ijms222011058
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
- id
- 43e17981-b3e3-4d57-9104-561dac37fc77
- date added to LUP
- 2021-10-26 13:56:11
- date last changed
- 2024-06-16 21:52:02
@article{43e17981-b3e3-4d57-9104-561dac37fc77,
abstract = {{<p>Intrinsically disordered proteins are involved in many biological processes such as signaling, regulation, and recognition. A common strategy to regulate their function is through phosphorylation, as it can induce changes in conformation, dynamics, and interactions with binding partners. Although phosphorylated intrinsically disordered proteins have received increased attention in recent years, a full understanding of the conformational and structural implications of phosphorylation has not yet been achieved. Here, we present all-atom molecular dynamics simulations of five disordered peptides originated from tau, statherin, and β-casein, in both phosphorylated and non-phosphorylated state, to compare changes in global dimensions and structural elements, in an attempt to gain more insight into the controlling factors. The changes are in qualitative agreement with experimental data, and we observe that the net charge is not enough to predict the impact of phosphorylation on the global dimensions. Instead, the distribution of phosphorylated and positively charged residues throughout the sequence has great impact due to the formation of salt bridges. In statherin, a preference for arginine–phosphoserine interaction over arginine–tyrosine accounts for a global expansion, despite a local contraction of the phosphorylated region, which implies that also non-charged residues can influence the effect of phosphorylation.</p>}},
author = {{Rieloff, Ellen and Skepö, Marie}},
issn = {{1661-6596}},
keywords = {{Force fields; Intrinsically disordered proteins; Phosphorylation}},
language = {{eng}},
month = {{10}},
number = {{20}},
publisher = {{MDPI AG}},
series = {{International Journal of Molecular Sciences}},
title = {{The effect of multisite phosphorylation on the conformational properties of intrinsically disordered proteins}},
url = {{http://dx.doi.org/10.3390/ijms222011058}},
doi = {{10.3390/ijms222011058}},
volume = {{22}},
year = {{2021}},
}