ArticleThe Journal of biological chemistry2013
Stereochemical determinants of C-terminal specificity in PDZ peptide-binding domains: a novel contribution of the carboxylate-binding loop.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 40 citations in OpenAlex.
- Sequence Engineering at Non-motif Modulator Residues Yields a Peptide That Effectively Targets a Single PDZ Protein in a Disease-relevant Cellular Context.Journal of molecular biology · 2026Article
- Sequence engineering at non-motif modulator residues yields a peptide that effectively targets a single PDZ protein in a disease-relevant cellular context.bioRxiv : the preprint server for biology · 2025Article
- DexDesign: an OSPREY-based algorithm for designing de novo D-peptide inhibitors.Protein engineering, design & selection : PEDS · 2024Article
- The conformation of the nSrc specificity-determining loop in the Src SH3 domain is modulated by a WX conserved sequence motif found in SH3 domains.Frontiers in molecular biosciences · 2024Article
- Additive energetic contributions of multiple peptide positions determine the relative promiscuity of viral and human sequences for PDZ domain targets.Protein science : a publication of the Protein Society · 2023Article
- Distinct Molecular Features of NleG Type 3 Secreted Effectors Allow for Different Roles during Citrobacter rodentium Infection in Mice.Infection and immunity · 2023Article
- Additive energetic contributions of multiple peptide positions determine the relative promiscuity of viral and human sequences for PDZ domain targets.bioRxiv : the preprint server for biology · 2023Article
- Tryptophan mutations in G3BP1 tune the stability of a cellular signaling hub by weakening transient interactions with Caprin1 and USP10.The Journal of biological chemistry · 2022Article
- Proteostasis Regulators in Cystic Fibrosis: Current Development and Future Perspectives.Journal of medicinal chemistry · 2022Review
- Domain Analysis and Motif Matcher (DAMM): A Program to Predict Selectivity Determinants inMolecules (Basel, Switzerland) · 2021Article
- 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
- Computational Analysis of Energy Landscapes Reveals Dynamic Features That Contribute to Binding of Inhibitors to CFTR-Associated Ligand.The journal of physical chemistry. B · 2019Article
- MotifAnalyzer-PDZ: A computational program to investigate the evolution of PDZ-binding target specificity.Protein science : a publication of the Protein Society · 2019Article
- Emerging Themes in PDZ Domain Signaling: Structure, Function, and Inhibition.International review of cell and molecular biology · 2019Review
- Cysteine modifiers suggest an allosteric inhibitory site on the CAL PDZ domain.Bioscience reports · 2018Article
- Optimization of the process of inverted peptides (PIPEBioorganic & medicinal chemistry letters · 2017Article
- Article
- PDZ Domain Recognition: Insight from Human Tax-Interacting Protein 1 (TIP-1) Interaction with Target Proteins.Biology · 2015Review
- Computational design of selective peptides to discriminate between similar PDZ domains in an oncogenic pathway.Journal of molecular biology · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
PDZ (PSD-95/Dlg/ZO-1) binding domains often serve as cellular traffic engineers, controlling the localization and activity of a wide variety of binding partners. As a result, they play important roles in both physiological and pathological processes. However, PDZ binding specificities overlap, allowing multiple PDZ proteins to mediate distinct effects on shared binding partners. For example, several PDZ domains bind the cystic fibrosis (CF) transmembrane conductance regulator (CFTR), an epithelial ion channel mutated in CF. Among these binding partners, the CFTR-associated ligand (CAL) facilitates post-maturational degradation of the channel and is thus a potential therapeutic target. Using iterative optimization, we previously developed a selective CAL inhibitor peptide (iCAL36). Here, we investigate the stereochemical basis of iCAL36 specificity. The crystal structure of iCAL36 in complex with the CAL PDZ domain reveals stereochemical interactions distributed along the peptide-binding cleft, despite the apparent degeneracy of the CAL binding motif. A critical selectivity determinant that distinguishes CAL from other CFTR-binding PDZ domains is the accommodation of an isoleucine residue at the C-terminal position (P(0)), a characteristic shared with the Tax-interacting protein-1. Comparison of the structures of these two PDZ domains in complex with ligands containing P(0) Leu or Ile residues reveals two distinct modes of accommodation for β-branched C-terminal side chains. Access to each mode is controlled by distinct residues in the carboxylate-binding loop. These studies provide new insights into the primary sequence determinants of binding motifs, which in turn control the scope and evolution of PDZ interactomes.
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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.