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Photo Marie Skepö

Marie Skepö

Professor

Photo Marie Skepö

The effect of multisite phosphorylation on the conformational properties of intrinsically disordered proteins

Author

  • Ellen Rieloff
  • Marie Skepö

Summary, in English

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.

Department/s

  • Computational Chemistry
  • LINXS - Institute of advanced Neutron and X-ray Science
  • eSSENCE: The e-Science Collaboration

Publishing year

2021-10-01

Language

English

Publication/Series

International Journal of Molecular Sciences

Volume

22

Issue

20

Document type

Journal article

Publisher

MDPI AG

Topic

  • Biological Sciences
  • Theoretical Chemistry (including Computational Chemistry)

Keywords

  • Force fields
  • Intrinsically disordered proteins
  • Phosphorylation

Status

Published

ISBN/ISSN/Other

  • ISSN: 1661-6596