Evidence map›Paper›PMID 30605082›Full record

ArticleeLife2019

Mechanisms of PDZ domain scaffold assembly illuminated by use of supported cell membrane sheets.

Simon Erlendsson, Thor Seneca Thorsen, Georges Vauquelin, Ina Ammendrup-Johnsen, Volker Wirth, Karen L Martinez, Kaare Teilum, Ulrik Gether, Kenneth Lindegaard Madsen

Open access · goldAbstract read
In one paragraph

Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.4field-weighted citation impact, top 23% of its field
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

12 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
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  7. Review
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  11. Binding Revisited-Avidity in Cellular Function and Signaling.Frontiers in molecular biosciences · 2020
    Review
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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

9 authors at 1 institution in 2 countries.

Simon Erlendsson *Molecular Neuropharmacology and Genetics Laboratory, Department of Neuroscience, Faculty of Health and Medical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0002-6378-870X
Thor Seneca Thorsen *Molecular Neuropharmacology and Genetics Laboratory, Department of Neuroscience, Faculty of Health and Medical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
Georges VauquelinMolecular and Biochemical Pharmacology, Department of Biotechnology, Free University Brussels (VUB), Brussels, Belgium.
Ina Ammendrup-JohnsenMolecular Neuropharmacology and Genetics Laboratory, Department of Neuroscience, Faculty of Health and Medical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
Volker WirthBionanotechnology and Nanomedicine Laboratory, Department of Chemistry, Nano-science Center, University of Copenhagen, Copenhagen, Denmark.
Karen L MartinezBionanotechnology and Nanomedicine Laboratory, Department of Chemistry, Nano-science Center, University of Copenhagen, Copenhagen, Denmark.
Kaare TeilumStructural Biology and NMR Laboratory, Department of Neuroscience, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0001-6919-1982
Ulrik GetherMolecular Neuropharmacology and Genetics Laboratory, Department of Neuroscience, Faculty of Health and Medical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
Kenneth Lindegaard MadsenMolecular Neuropharmacology and Genetics Laboratory, Department of Neuroscience, Faculty of Health and Medical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0001-9274-6691
University of Copenhagen · DK

Funding

STRUCTURE/FUNCTION OF THE HUMAN DOPAMINE TRANSPORTERP01DA012408 · NIDA · WEILL MEDICAL COLL OF CORNELL UNIV · PI WEINSTEIN, HAREL · 1999 to 2015
$14.2M
Lundbeckfonden Center for Biomembranes in NanomedicineNIDA NIH HHS P01 DA012408NIH HHS P01 DA 12408University of Copenhagen BioScaRT Programof ExcellenceUniversity of Copenhagen UNIK Center for Synthetic Biology
6 · The paper itself

Abstract

PDZ domain scaffold proteins are molecular modules orchestrating cellular signalling in space and time. Here, we investigate assembly of PDZ scaffolds using supported cell membrane sheets, a unique experimental setup enabling direct access to the intracellular face of the cell membrane. Our data demonstrate how multivalent protein-protein and protein-lipid interactions provide critical avidity for the strong binding between the PDZ domain scaffold proteins, PICK1 and PSD-95, and their cognate transmembrane binding partners. The kinetics of the binding were remarkably slow and binding strength two-three orders of magnitude higher than the intrinsic affinity for the isolated PDZ interaction. Interestingly, discrete changes in the intrinsic PICK1 PDZ affinity did not affect overall binding strength but instead revealed dual scaffold modes for PICK1. Our data supported by simulations suggest that intrinsic PDZ domain affinities are finely tuned and encode specific cellular responses, enabling multiplexed cellular functions of PDZ scaffolds.

Indexed as

PDZ DomainsAllosteric SiteAmino Acid MotifsAnimalsBinding SitesCell MembraneCytoskeletal ProteinsDisks Large Homolog 4 ProteinHEK293 CellsHippocampusHumansKineticsLigandsMutationNeuronsProtein BindingCytoskeletal ProteinsDisks Large Homolog 4 ProteinDlg4 protein, ratLigandsPICK1 protein, ratRecombinant Proteinsbiochemistrychemical biologynonepost synaptic densityscaffold proteinssynaptic structure

Identifiers

PMID30605082
PMCPMC6345565
OpenAlexW2906994560

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.