ArticlePLoS computational biology2012
Beyond the binding site: the role of the β₂-β₃ loop and extra-domain structures in PDZ domains.
Article in PLoS computational biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Seven complete comparative maps of allosteric mutations in a protein family.Nature communications · 2026Article
- Allosteric and energetic remodeling of a PDZ domain by protein domain extensions.Nature communications · 2026Article
- A complete map of specificity encoding for a partially fuzzy protein interaction.bioRxiv : the preprint server for biology · 2024Article
- Resonance assignment of the Shank1 PDZ domain.Biomolecular NMR assignments · 2022Article
- Phosphorylation-induced changes in the PDZ domain of Dishevelled 3.Scientific reports · 2021Article
- Divergent Evolution of a Protein-Protein Interaction Revealed through Ancestral Sequence Reconstruction and Resurrection.Molecular biology and evolution · 2021Article
- Ensemble-Based Analysis of the Dynamic Allostery in the PSD-95 PDZ3 Domain in Relation to the General Variability of PDZ Structures.International journal of molecular sciences · 2020Article
- The Conformational Plasticity Vista of PDZ Domains.Life (Basel, Switzerland) · 2020Review
- Dishevelled-3 conformation dynamics analyzed by FRET-based biosensors reveals a key role of casein kinase 1.Nature communications · 2019Article
- Emerging Themes in PDZ Domain Signaling: Structure, Function, and Inhibition.International review of cell and molecular biology · 2019Review
- Hidden electrostatic basis of dynamic allostery in a PDZ domain.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Contrasting roles of dynamics in protein allostery: NMR and structural studies of CheY and the third PDZ domain from PSD-95.Biophysical reviews · 2015Review
- Peptide Binding to a PDZ Domain by Electrostatic Steering via Nonnative Salt Bridges.Biophysical journal · 2015Article
- Protein interacting with C-kinase 1 (PICK1) binding promiscuity relies on unconventional PSD-95/discs-large/ZO-1 homology (PDZ) binding modes for nonclass II PDZ ligands.The Journal of biological chemistry · 2014Article
- Post-translational modifications modulate ligand recognition by the third PDZ domain of the MAGUK protein PSD-95.PloS one · 2014Article
- Ligand-induced dynamic changes in extended PDZ domains from NHERF1.Journal of molecular biology · 2013Article
- The interconversion between a flexible β-sheet and a fibril β-arrangement constitutes the main conformational event during misfolding of PSD95-PDZ3 domain.Biophysical journal · 2012Article
- Plasticity of PDZ domains in ligand recognition and signaling.FEBS letters · 2012Review
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3 authors.
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No grant is acknowledged in the PubMed record.
Abstract
A general paradigm to understand protein function is to look at properties of isolated well conserved domains, such as SH3 or PDZ domains. While common features of domain families are well understood, the role of subtle differences among members of these families is less clear. Here, molecular dynamics simulations indicate that the binding mechanism in PSD95-PDZ3 is critically regulated via interactions outside the canonical binding site, involving both the poorly conserved β₂-β₃ loop and an extra-domain helix. Using the CRIPT peptide as a prototypical ligand, our simulations suggest that a network of salt-bridges between the ligand and this loop is necessary for binding. These contacts interconvert between each other on a time scale of a few tens of nanoseconds, making them elusive to X-ray crystallography. The loop is stabilized by an extra-domain helix. The latter influences the global dynamics of the domain, considerably increasing binding affinity. We found that two key contacts between the helix and the domain, one involving the β₂-β₃ loop, provide an atomistic interpretation of the increased affinity. Our analysis indicates that both extra-domain segments and loosely conserved regions play critical roles in PDZ binding affinity and specificity.
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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.