Dynamic interaction network involving the conserved intrinsically disordered regions in human eIF5

We reveal presence of intrinsically disordered regions in human kinome and build a kinase–kinase interaction network identifying a novel SRC–SMAD relationship.

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Intrinsically disordered regions of Tristetraprolin and DCP2 directly interact to mediate decay of ARE-mRNA

10.1101/2021.11.07.467627 ◽

2021 ◽

Author(s):

Vincent D. Maciej ◽

Nevena Mateva ◽

Theresa Dittmers ◽

Sutapa Chakrabarti

Keyword(s):

Mrna Decay ◽

Rna Binding ◽

Weak Interactions ◽

Direct Interaction ◽

Interaction Network ◽

Cellular Interaction ◽

Intrinsically Disordered ◽

Intrinsically Disordered Regions ◽

Disordered Regions

The RNA binding protein Tristetraprolin (TTP) is a potent activator of mRNA decay, specifically for transcripts bearing AU-rich elements (AREs) in their 3'-untranslated regions. TTP functions as a mediator for mRNA decay by interacting with the decay machinery and recruiting it to the target ARE-mRNA. In this study, we report a weak, but direct interaction between TTP and the human decapping enzyme DCP2, which impacts the stability of ARE-transcripts. The TTP-DCP2 interaction is unusual as it involves intrinsically disordered regions (IDRs) of both binding partners. We show that the IDR of DCP2 has a propensity for oligomerization and liquid-liquid phase separation (LLPS) in vitro. Binding of TTP to DCP2 leads to its partitioning into phase-separated droplets formed by DCP2, suggesting that molecular crowding might facilitate the weak interaction between the two proteins and enable assembly of a decapping-competent mRNA-protein complex on TTP-bound transcripts in cells. Our studies underline the role of weak interactions in the cellular interaction network and their contribution towards cellular functionality.

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Faculty Opinions recommendation of Evaluation of sequence features from intrinsically disordered regions for the estimation of protein function.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718294858.793491709 ◽

2014 ◽

Author(s):

Vladimir Uversky

Keyword(s):

Protein Function ◽

Sequence Features ◽

Intrinsically Disordered ◽

Intrinsically Disordered Regions ◽

Disordered Regions

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Faculty Opinions recommendation of Nonoptimal codon usage influences protein structure in intrinsically disordered regions.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725529522.793507335 ◽

2015 ◽

Author(s):

Vladimir Uversky

Keyword(s):

Protein Structure ◽

Codon Usage ◽

Intrinsically Disordered ◽

Intrinsically Disordered Regions ◽

Disordered Regions

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Faculty Opinions recommendation of Codon usage is less optimized in eukaryotic gene segments encoding intrinsically disordered regions than in those encoding structural domains.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726911331.793526186 ◽

2017 ◽

Author(s):

Vladimir Uversky

Keyword(s):

Codon Usage ◽

Structural Domains ◽

Intrinsically Disordered ◽

Intrinsically Disordered Regions ◽

Eukaryotic Gene ◽

Disordered Regions

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Faculty Opinions recommendation of Intrinsically disordered regions direct transcription factor in vivo binding specificity.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.738147787.793576666 ◽

2020 ◽

Author(s):

Andrew D Sharrocks

Keyword(s):

Transcription Factor ◽

Binding Specificity ◽

Direct Transcription ◽

In Vivo Binding ◽

Intrinsically Disordered ◽

Intrinsically Disordered Regions ◽

Disordered Regions

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Faculty Opinions recommendation of Intrinsically disordered regions direct transcription factor in vivo binding specificity.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.738147787.793575950 ◽

2020 ◽

Author(s):

Vladimir Uversky

Keyword(s):

Transcription Factor ◽

Binding Specificity ◽

Direct Transcription ◽

In Vivo Binding ◽

Intrinsically Disordered ◽

Intrinsically Disordered Regions ◽

Disordered Regions

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The C-terminal tail extension of myosin 16 possesses intrinsically disordered regions as molten globule and interacts with the N-terminal ankyrin

Journal of Biological Chemistry ◽

10.1016/j.jbc.2021.100716 ◽

2021 ◽

pp. 100716

Author(s):

Elek Telek ◽

Kristóf Karádi ◽

József Kardos ◽

András Kengyel ◽

Zsuzsanna Fekete ◽

...

Keyword(s):

Molten Globule ◽

Intrinsically Disordered ◽

Intrinsically Disordered Regions ◽

Disordered Regions

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Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation

Nature Communications ◽

10.1038/s41467-021-21035-4 ◽

2021 ◽

Vol 12 (1) ◽

Cited By ~ 3

Author(s):

Vikas A. Tillu ◽

James Rae ◽

Ya Gao ◽

Nicholas Ariotti ◽

Matthias Floetenmeyer ◽

...

Keyword(s):

Electrostatic Interactions ◽

Membrane Lipid ◽

Membrane Curvature ◽

Caveolin 1 ◽

Intrinsically Disordered ◽

Intrinsically Disordered Regions ◽

Solution Generation ◽

Endosomal System ◽

Disordered Regions

AbstractCaveolae are spherically shaped nanodomains of the plasma membrane, generated by cooperative assembly of caveolin and cavin proteins. Cavins are cytosolic peripheral membrane proteins with negatively charged intrinsically disordered regions that flank positively charged α-helical regions. Here, we show that the three disordered domains of Cavin1 are essential for caveola formation and dynamic trafficking of caveolae. Electrostatic interactions between disordered regions and α-helical regions promote liquid-liquid phase separation behaviour of Cavin1 in vitro, assembly of Cavin1 oligomers in solution, generation of membrane curvature, association with caveolin-1, and Cavin1 recruitment to caveolae in cells. Removal of the first disordered region causes irreversible gel formation in vitro and results in aberrant caveola trafficking through the endosomal system. We propose a model for caveola assembly whereby fuzzy electrostatic interactions between Cavin1 and caveolin-1 proteins, combined with membrane lipid interactions, are required to generate membrane curvature and a metastable caveola coat.

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