Evidence map›Paper›PMID 36157580›Full record

ArticleiScience2022

Determinants of affinity, specificity, and phase separation in a supramodule from Post-synaptic density protein 95.

Louise Laursen, Raviteja Inturi, Søren Østergaard, Per Jemth

Abstract read
In one paragraph

Article in iScience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Louise LaursenDepartment of Medical Biochemistry and Microbiology, Uppsala University, BMC Box 582, 75123 Uppsala, Sweden.
Raviteja InturiDepartment of Medical Biochemistry and Microbiology, Uppsala University, BMC Box 582, 75123 Uppsala, Sweden.
Søren ØstergaardGlobal Research Technology, Novo Nordisk A/S, Novo Nordisk Research Park, 2760 Maalov, Denmark.
Per JemthDepartment of Medical Biochemistry and Microbiology, Uppsala University, BMC Box 582, 75123 Uppsala, Sweden.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The post-synaptic density (PSD) is a phase-separated membraneless compartment of proteins including PSD-95 that undergoes morphological alteration in response to synaptic activity. Here, we investigated the interactome of a three-domain supramodule, PDZ3-SH3-GK (PSG) from PSD-95 using bioinformatics to identify potential binding partners, and biophysical methods to characterize the interaction with peptides from these proteins. PSG and the single PDZ3 domain bound similar peptides, but with different specificity. Furthermore, we found that the protein ADGRB1 formed liquid droplets with the PSG supramodule, extending the model for PSD formation. Moreover, certain mutations, introduced outside of the binding pocket in PDZ3, increased the affinity and specificity of the interaction and the size of liquid droplets. Other mutations within the ligand binding pocket lead to a new binding motif specificity. Our results show how the context in terms of supertertiary structure modulates affinity, specificity, and phase separation, and how these properties can evolve by point mutation.

Indexed as

BiophysicsProteinProtein structure aspects

Identifiers

PMID36157580
PMCPMC9490041

What OpenQuestion holds

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Registered trials

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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 OpenQuestion graph.