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Cited by 322Protein Structure and DynamicsAdvanced Proteomics Techniques and ApplicationsProtein Kinase Regulation and GTPase Signaling

Phosphorylation in protein-protein binding: effect on stability and function

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Nishi, Hafumi, Hashimoto, Kosuke, Panchenko, Anna R.·2011·Structure
DOI 10.1016/j.str.2011.09.021PMC PMC3240861
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Abstract

Posttranslational modifications offer a dynamic way to regulate protein activity, subcellular localization, and stability. Here we estimate the effect of phosphorylation on protein binding and function for different types of complexes from human proteome. We find that phosphorylation sites tend to be located on binding interfaces in heterooligomeric and weak transient homooligomeric complexes. Analysis of molecular mechanisms of phosphorylation shows that phosphorylation may modulate the strength of interactions directly on interfaces and that binding hotspots tend to be phosphorylated in heterooligomers. Although the majority of complexes do not show significant estimated stability differences upon phosphorylation or dephosphorylation, for about one-third of all complexes it causes relatively large changes in binding energy. We discuss the cases where phosphorylation mediates the complex formation and regulates the function. We show that phosphorylation sites are more likely to be evolutionary conserved than other interfacial residues.

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  • PTMs are known to function as molecular switches by affecting protein-protein interactions.

    “PTMs are known to function as molecular switches by affecting protein-protein interactions (Chen, Liu et al., 2020, Nishi, Hashimoto et al., 2011).”

    From SHARPIN S146 phosphorylation mediates ARP2/3 interaction, cancer cell invasion and metastasis (2022) · cites this paper as Nishi, Hashimoto et al., 2011

    The Introduction says phosphorylation can modulate the nature and strength of protein-protein interactions, and the Discussion describes reversible phosphorylation as a mechanism for regulating protein activity. This supports the switch-like mechanism for phosphorylation, but the paper does not establish it for PTMs generally. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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Sorted by citations

Authors
Nishi, H., Hashimoto, K., & Panchenko, A. R.
Affiliations
National Institutes of Health (US)
Corresponding author
Panchenko, Anna R.
ORCID
Venue
Structure
Publisher
Elsevier BV
Published
2011-12
Volume
19
Issue
12
Pages
1807-1815
ISSN
0969-2126 (ISSN-L)
DOI
10.1016/j.str.2011.09.021
PMC
PMC3240861
OpenAlex
W2010516785
Cited by
322
References
5
Citations by year
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FWCI
4.87
Type
journal article
Language
en
Open access
Licence
Locations
  • Structure (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (Z99 LM999999, Z99 HL999999, Z99 MH999999, Z99CL999999)
  • U.S. National Library of Medicine
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
protein phosphorylation, protein-protein binding, binding interface, protein complex stability, binding energy, binding hot spots, post-translational modification, dephosphorylation, evolutionary conservation, human proteome
MeSH terms
Binding Sites, Humans, Phosphorylation, Protein Conformation, Proteins, Evolution, Molecular, Proteome

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