ArticleProceedings of the National Academy of Sciences of the United States of America2017
Conserved salt-bridge competition triggered by phosphorylation regulates the protein interactome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Raf kinase inhibitor protein combined with phosphorylated extracellular signal-regulated kinase offers valuable prognosis in gastrointestinal stromal tumor.World journal of gastroenterology · 2023Trial
- Mechanistic design of cell-penetrating disruptors for phospho-dependent TACC3-CHC interaction.Structure (London, England : 1993) · 2026Article
- Protein Kinase A Phosphorylates a Conformationally High-energy State of Raf Kinase Inhibitory Protein.Journal of molecular biology · 2025Article
- Article
- Two Cysteines in Raf Kinase Inhibitor Protein Make Differential Contributions to Structural Dynamics In Vitro.Molecules (Basel, Switzerland) · 2025Article
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- Review
- The deficiency of poly-β-1,6-N-acetyl-glucosamine deacetylase trigger A. baumannii to convert to biofilm-independent colistin-tolerant cells.Scientific reports · 2023Article
- A Zn-dependent structural transition of SOD1 modulates its ability to undergo phase separation.The EMBO journal · 2023Article
- Raf Kinase Inhibitory Protein regulates the cAMP-dependent protein kinase signaling pathway through a positive feedback loop.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- α-Helix stabilization by co-operative side chain charge-reinforced interactions to phosphoserine in a basic kinase-substrate motif.The Biochemical journal · 2022Article
- Harnessing RKIP to Combat Heart Disease and Cancer.Cancers · 2022Review
- Review
- Rely on Each Other: DNA Binding Cooperativity Shapes p53 Functions in Tumor Suppression and Cancer Therapy.Cancers · 2021Review
- Phosphoserine inhibits neighboring arginine methylation in the RKS motif of histone H3.Archives of biochemistry and biophysics · 2021Article
- Methylation-directed glycosylation of chromatin factors represses retrotransposon promoters.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- PEBP1/RKIP behavior: a mirror of actin-membrane organization.Cellular and molecular life sciences : CMLS · 2020Article
- Article
- Triple arginines as molecular determinants for pentameric assembly of the intracellular domain of 5-HTThe Journal of general physiology · 2019Article
- Rational design of a heterotrimeric G protein α subunit with artificial inhibitor sensitivity.The Journal of biological chemistry · 2019Article
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Authors and funding
13 authors.
Funding
Abstract
Phosphorylation is a major regulator of protein interactions; however, the mechanisms by which regulation occurs are not well understood. Here we identify a salt-bridge competition or "theft" mechanism that enables a phospho-triggered swap of protein partners by Raf Kinase Inhibitory Protein (RKIP). RKIP transitions from inhibiting Raf-1 to inhibiting G-protein-coupled receptor kinase 2 upon phosphorylation, thereby bridging MAP kinase and G-Protein-Coupled Receptor signaling. NMR and crystallography indicate that a phosphoserine, but not a phosphomimetic, competes for a lysine from a preexisting salt bridge, initiating a partial unfolding event and promoting new protein interactions. Structural elements underlying the theft occurred early in evolution and are found in 10% of homo-oligomers and 30% of hetero-oligomers including Bax, Troponin C, and Early Endosome Antigen 1. In contrast to a direct recognition of phosphorylated residues by binding partners, the salt-bridge theft mechanism represents a facile strategy for promoting or disrupting protein interactions using solvent-accessible residues, and it can provide additional specificity at protein interfaces through local unfolding or conformational change.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.