ArticlePloS one2011
Genome-wide analysis of PDZ domain binding reveals inherent functional overlap within the PDZ interaction network.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- The PDLIM family of actin-associated proteins and their emerging role in membrane trafficking.Biochemical Society transactions · 2023Review
- An interaction between OTULIN and SCRIB uncovers roles for linear ubiquitination in planar cell polarity.Disease models & mechanisms · 2023Article
- Structural characterization and computational analysis of PDZ domains in Monosiga brevicollis.Protein science : a publication of the Protein Society · 2020Article
- Specificity in PDZ-peptide interaction networks: Computational analysis and review.Journal of structural biology: X · 2020Review
- MotifAnalyzer-PDZ: A computational program to investigate the evolution of PDZ-binding target specificity.Protein science : a publication of the Protein Society · 2019Article
- PDZ Domains as Drug Targets.Advanced therapeutics · 2019Review
- Structure function relations in PDZ-domain-containing proteins: Implications for protein networks in cellular signalling.Journal of biosciences · 2018Review
- modPDZpep: a web resource for structure based analysis of human PDZ-mediated interaction networks.Biology direct · 2016Article
- Towards the construction of an interactome for Human WD40 protein family.Bioinformation · 2016Article
- Computational design of selective peptides to discriminate between similar PDZ domains in an oncogenic pathway.Journal of molecular biology · 2015Article
- The human PDZome: a gateway to PSD95-Disc large-zonula occludens (PDZ)-mediated functions.Molecular & cellular proteomics : MCP · 2013Article
- Synergistic effect of the PDZ and p85β-binding domains of the NS1 protein on virulence of an avian H5N1 influenza A virus.Journal of virology · 2013Article
- Article
- An in silico analysis of the binding modes and binding affinities of small molecule modulators of PDZ-peptide interactions.PloS one · 2013Article
- Prevalence, specificity and determinants of lipid-interacting PDZ domains from an in-cell screen and in vitro binding experiments.PloS one · 2013Article
- Computational design of a PDZ domain peptide inhibitor that rescues CFTR activity.PLoS computational biology · 2012Article
- Sequence-specific long range networks in PSD-95/discs large/ZO-1 (PDZ) domains tune their binding selectivity.The Journal of biological chemistry · 2011Article
- Evolutionarily conserved bias of amino-acid usage refines the definition of PDZ-binding motif.BMC genomics · 2011Article
- Putting into practice domain-linear motif interaction predictions for exploration of protein networks.PloS one · 2011Article
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Authors and funding
4 authors.
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Abstract
Binding selectivity and cross-reactivity within one of the largest and most abundant interaction domain families, the PDZ family, has long been enigmatic. The complete human PDZ domain complement (the PDZome) consists of 267 domains and we applied here a Bayesian selectivity model to predict hundreds of human PDZ domain interactions, using target sequences of 22,997 non-redundant proteins. Subsequent analysis of these binding scores shows that PDZs can be divided into two genome-wide clusters that coincide well with the division between canonical class 1 and 2 PDZs. Within the class 1 PDZs we observed binding overlap at unprecedented levels, mediated by two residues at positions 1 and 5 of the second α-helix of the binding pocket. Eight PDZ domains were subsequently selected for experimental binding studies and to verify the basics of our predictions. Overall, the PDZ domain class 1 cross-reactivity identified here implies that auxiliary mechanisms must be in place to overcome this inherent functional overlap and to minimize cross-selectivity within the living cell. Indeed, when we superimpose PDZ domain binding affinities with gene ontologies, network topology data and the domain position within a PDZ superfamily protein, functional overlap is minimized and PDZ domains position optimally in the binding space. We therefore propose that PDZ domain selectivity is achieved through cellular context rather than inherent binding specificity.
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