scholarly journals Ligand binding by PDZ domains

BioFactors ◽  
2012 ◽  
Vol 38 (5) ◽  
pp. 338-348 ◽  
Author(s):  
Celestine N. Chi ◽  
Anders Bach ◽  
Kristian Strømgaard ◽  
Stefano Gianni ◽  
Per Jemth
Keyword(s):  
Ligand Binding ◽  
Pdz Domains

scholarly journals Interdependence of intra- and inter-domain motions in the PSD-95 PDZ12 tandem

2019 ◽  
Author(s):  
Bertalan Kovács ◽  
Nóra Zajácz-Epresi ◽  
Zoltán Gáspári
Keyword(s):  
Ligand Binding ◽  
Structural Changes ◽  
Regulatory Region ◽  
Peptide Ligand ◽  
Pdz Domains ◽  
Specific Domain ◽  
Interatomic Distances ◽  
Conformational Ensembles ◽  
Domain Motions ◽  
Partner Proteins

AbstractPSD-95 is the most abundant scaffold protein in the postsynaptic density of neurons. Its two N-terminal PDZ domains form an autonomous structural unit and their interdomain orientation and dynamics was shown to be dependent on binding to various partner proteins. To understand the mechanistic details of the effect of ligand binding on interdomain structure and dynamics, we generated conformational ensembles using experimentally determined NOE interatomic distances and S2order parameters, available from the literature. In our approach no explicit restraints between the two domains were used and their fast dynamics was also treated independently. We found that intradomain structural changes induced by ligand binding have a profound effect on the interfaces where interdomain contacts can be formed, modulating the probability of the occurrence of specific domain-domain orientations. Our results suggest that the β2-β3 loop in the PDZ domains is a key regulatory region that, through interacting with the upstream residues of the C-terminal peptide ligand, influences both intradomain motions and supramodular rearrangement.

scholarly journals Ensemble-Based Analysis of the Dynamic Allostery in the PSD-95 PDZ3 Domain in Relation to the General Variability of PDZ Structures

2020 ◽  
Vol 21 (21) ◽  
pp. 8348
Author(s):  
Dániel Dudola ◽  
Anett Hinsenkamp ◽  
Zoltán Gáspári
Keyword(s):  
Ligand Binding ◽  
General Feature ◽  
Allosteric Modulation ◽  
Side Chain ◽  
Ligand Specificity ◽  
Structural Rearrangements ◽  
Pdz Domains ◽  
Postsynaptic Protein ◽  
Conformational Diversity ◽  
Structural Ensembles

PDZ domains are abundant interaction hubs found in a number of different proteins and they exhibit characteristic differences in their structure and ligand specificity. Their internal dynamics have been proposed to contribute to their biological activity via changes in conformational entropy upon ligand binding and allosteric modulation. Here we investigate dynamic structural ensembles of PDZ3 of the postsynaptic protein PSD-95, calculated based on previously published backbone and side-chain S2 order parameters. We show that there are distinct but interdependent structural rearrangements in PDZ3 upon ligand binding and the presence of the intramolecular allosteric modulator helix α3. We have also compared these rearrangements in PDZ1-2 of PSD-95 and the conformational diversity of an extended set of PDZ domains available in the PDB database. We conclude that although the opening-closing rearrangement, occurring upon ligand binding, is likely a general feature for all PDZ domains, the conformer redistribution upon ligand binding along this mode is domain-dependent. Our findings suggest that the structural and functional diversity of PDZ domains is accompanied by a diversity of internal motional modes and their interdependence.

scholarly journals Synaptic MAGUK Multimer Formation Is Mediated by PDZ Domains and Promoted by Ligand Binding

2013 ◽  
Vol 20 (8) ◽  
pp. 1044-1054 ◽  
Author(s):  
Nils Rademacher ◽  
Stella-Amrei Kunde ◽  
Vera M. Kalscheuer ◽  
Sarah A. Shoichet
Keyword(s):  
Ligand Binding ◽  
Pdz Domains

scholarly journals Ligand binding of PDZ domains has various roles in the synaptic clustering of SAP102 and PSD-95

2013 ◽  
Vol 533 ◽  
pp. 44-49 ◽  
Author(s):  
Keiichiro Minatohara ◽  
Sho-hei Ichikawa ◽  
Tatsuya Seki ◽  
Yoshinori Fujiyoshi ◽  
Tomoko Doi
Keyword(s):  
Ligand Binding ◽  
Pdz Domains ◽  
Synaptic Clustering

scholarly journals Ligand binding to the PDZ domains of postsynaptic density protein 95

2016 ◽  
Vol 29 (5) ◽  
pp. 169-175 ◽  
Author(s):  
Angelo Toto ◽  
Søren W. Pedersen ◽  
O. Andreas Karlsson ◽  
Griffin E. Moran ◽  
Eva Andersson ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Postsynaptic Density ◽  
Pdz Domains ◽  
Postsynaptic Density Protein

CarR, a MarR-family regulator from Corynebacterium glutamicum, modulated antibiotic and aromatic compound resistance

2019 ◽  
Vol 476 (21) ◽  
pp. 3141-3159 ◽  
Author(s):  
Meiru Si ◽  
Can Chen ◽  
Zengfan Wei ◽  
Zhijin Gong ◽  
GuiZhi Li ◽  
...  
Keyword(s):  
Stress Response ◽  
Ligand Binding ◽  
Corynebacterium Glutamicum ◽  
Conformational Changes ◽  
Cysteine Oxidation ◽  
Transcriptional Regulatory ◽  
Ligand Free ◽  
Redox Sensing

Abstract MarR (multiple antibiotic resistance regulator) proteins are a family of transcriptional regulators that is prevalent in Corynebacterium glutamicum. Understanding the physiological and biochemical function of MarR homologs in C. glutamicum has focused on cysteine oxidation-based redox-sensing and substrate metabolism-involving regulators. In this study, we characterized the stress-related ligand-binding functions of the C. glutamicum MarR-type regulator CarR (C. glutamicum antibiotic-responding regulator). We demonstrate that CarR negatively regulates the expression of the carR (ncgl2886)–uspA (ncgl2887) operon and the adjacent, oppositely oriented gene ncgl2885, encoding the hypothetical deacylase DecE. We also show that CarR directly activates transcription of the ncgl2882–ncgl2884 operon, encoding the peptidoglycan synthesis operon (PSO) located upstream of carR in the opposite orientation. The addition of stress-associated ligands such as penicillin and streptomycin induced carR, uspA, decE, and PSO expression in vivo, as well as attenuated binding of CarR to operator DNA in vitro. Importantly, stress response-induced up-regulation of carR, uspA, and PSO gene expression correlated with cell resistance to β-lactam antibiotics and aromatic compounds. Six highly conserved residues in CarR were found to strongly influence its ligand binding and transcriptional regulatory properties. Collectively, the results indicate that the ligand binding of CarR induces its dissociation from the carR–uspA promoter to derepress carR and uspA transcription. Ligand-free CarR also activates PSO expression, which in turn contributes to C. glutamicum stress resistance. The outcomes indicate that the stress response mechanism of CarR in C. glutamicum occurs via ligand-induced conformational changes to the protein, not via cysteine oxidation-based thiol modifications.

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