Evidence map›Paper›PMID 29061852›Full record

ArticleThe Journal of biological chemistry2017

Structural basis for the differential interaction of Scribble PDZ domains with the guanine nucleotide exchange factor β-PIX.

Krystle Y B Lim, Nathan J Gödde, Patrick O Humbert, Marc Kvansakul

Open access · hybridAbstract readComparative Study
In one paragraph

Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

16 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. Article
  3. Scribble scrambles parathyroid hormone receptor interactions to regulate phosphate and vitamin D homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  4. Viral subversion of the cell polarity regulator Scribble.Biochemical Society transactions · 2023
    Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Sorting of cadherin-catenin-associated proteins into individual clusters.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. PDZ Domains as Drug Targets.Advanced therapeutics · 2019
    Review
  16. Review
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 at 2 institutions in 2 countries.

Krystle Y B LimFrom the Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086.
Nathan J GöddeFrom the Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086.
Patrick O HumbertFrom the Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, p.humbert@latrobe.edu.au.
Marc KvansakulFrom the Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, m.kvansakul@latrobe.edu.au.ORCID 0000-0003-2639-2498
La Trobe University · AUThe University of Melbourne · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Scribble is a highly conserved protein regulator of cell polarity that has been demonstrated to function as a tumor suppressor or, conversely, as an oncogene in a context-dependent manner, and it also controls many physiological processes ranging from immunity to memory. Scribble consists of a leucine-rich repeat domain and four PDZ domains, with the latter being responsible for most of Scribble's complex formation with other proteins. Given the similarities of the Scribble PDZ domain sequences in their binding grooves, it is common for these domains to show overlapping preferences for the same ligand. Yet, Scribble PDZ domains can still exhibit unique binding profiles toward other ligands. This raises the fundamental question as to how these PDZ domains discriminate ligands and exert specificities in Scribble complex formation. To better understand how Scribble PDZ domains direct cell polarity signaling, we investigated here their interactions with the well-characterized Scribble binding partner β-PIX, a guanine nucleotide exchange factor. We report the interaction profiles of all isolated Scribble PDZ domains with a β-PIX peptide. We show that Scribble PDZ1 and PDZ3 are the major interactors with β-PIX and reveal a distinct binding hierarchy in the interactions between the individual Scribble PDZ domains and β-PIX. Furthermore, using crystal structures of PDZ1 and PDZ3 bound to β-PIX, we define the structural basis for Scribble's ability to specifically engage β-PIX via its PDZ domains and provide a mechanistic platform for understanding Scribble-β-PIX-coordinated cellular functions such as directional cell migration.

Indexed as

Models, MolecularAmino Acid SequenceAmino Acid SubstitutionBinding SitesCalorimetryConserved SequenceCrystallography, X-RayHEK293 CellsHumansKineticsLigandsMembrane ProteinsMutationPDZ DomainsPeptide FragmentsProtein ConformationARHGEF7 protein, humanLigandsMembrane ProteinsPeptide FragmentsRecombinant Fusion ProteinsRecombinant ProteinsRho Guanine Nucleotide Exchange FactorsSCRIB protein, humanTumor Suppressor Proteinscell migrationcell polarityPDZ domainScribbleX-ray crystallographyβ-pix

Identifiers

PMID29061852
PMCPMC5733582
OpenAlexW2766865656

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.