ArticleThe Journal of biological chemistry2011
Sequence-specific long range networks in PSD-95/discs large/ZO-1 (PDZ) domains tune their binding selectivity.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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.
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.
Who cites it
44 citing papers in PubMed.
- Robust SH2 binding affinity indicates minimal SH3-to-SH2 communication in Grb2.Biology direct · 2026Article
- Evolution of the Tri-PDZ Domain in PSD95 (DLG-4 Gene).Molecular biology and evolution · 2025Article
- Allosteric modulation of Grb2 drives ligand-dependent signal responses.Biology direct · 2025Article
- Simultaneous Native Mass Spectrometry Analysis of Single and Double Mutants To Probe Lipid Binding to Membrane Proteins.Analytical chemistry · 2024Article
- SIMULTANEOUS NATIVE MASS SPECTROMETRY ANALYSIS OF SINGLE AND DOUBLE MUTANTS TO PROBE LIPID BINDING TO MEMBRANE PROTEINS.bioRxiv : the preprint server for biology · 2023Article
- An intramolecular energetic network regulates ligand recognition in a SH2 domain.Protein science : a publication of the Protein Society · 2023Article
- Investigating the allosteric response of the PICK1 PDZ domain to different ligands with all-atom simulations.Protein science : a publication of the Protein Society · 2022Article
- Determinants of affinity, specificity, and phase separation in a supramodule from Post-synaptic density protein 95.iScience · 2022Article
- Structure-mechanics statistical learning uncovers mechanical relay in proteins.Chemical science · 2022Article
- Allosterism in the PDZ Family.International journal of molecular sciences · 2022Review
- Exosite binding modulates the specificity of the immunomodulatory enzyme ScpA, a C5a inactivating bacterial protease.Computational and structural biotechnology journal · 2022Article
- Experimental Characterization of the Interaction between the N-Terminal SH3 Domain of Crkl and C3G.International journal of molecular sciences · 2021Article
- Double Mutant Cycles as a Tool to Address Folding, Binding, and Allostery.International journal of molecular sciences · 2021Review
- 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
- Peptide Gaussian accelerated molecular dynamics (Pep-GaMD): Enhanced sampling and free energy and kinetics calculations of peptide binding.The Journal of chemical physics · 2020Article
- Supertertiary protein structure affects an allosteric network.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The Conformational Plasticity Vista of PDZ Domains.Life (Basel, Switzerland) · 2020Review
- Understanding the Mechanism of Recognition of Gab2 by the N-SH2 Domain of SHP2.Life (Basel, Switzerland) · 2020Article
- Functional interplay between protein domains in a supramodular structure involving the postsynaptic density protein PSD-95.The Journal of biological chemistry · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein-protein interactions mediated by modular protein domains are critical for cell scaffolding, differentiation, signaling, and ultimately, evolution. Given the vast number of ligands competing for binding to a limited number of domain families, it is often puzzling how specificity can be achieved. Selectivity may be modulated by intradomain allostery, whereby a remote residue is energetically connected to the functional binding site via side chain or backbone interactions. Whereas several energetic pathways, which could mediate intradomain allostery, have been predicted in modular protein domains, there is a paucity of experimental data to validate their existence and roles. Here, we have identified such functional energetic networks in one of the most common protein-protein interaction modules, the PDZ domain. We used double mutant cycles involving site-directed mutagenesis of both the PDZ domain and the peptide ligand, in conjunction with kinetics to capture the fine energetic details of the networks involved in peptide recognition. We performed the analysis on two homologous PDZ-ligand complexes and found that the energetically coupled residues differ for these two complexes. This result demonstrates that amino acid sequence rather than topology dictates the allosteric pathways. Furthermore, our data support a mechanism whereby the whole domain and not only the binding pocket is optimized for a specific ligand. Such cross-talk between binding sites and remote residues may be used to fine tune target selectivity.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.