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Ligand‐dependent intra‐ and interdomain motions in the PDZ12 tandem regulate binding interfaces in postsynaptic density protein‐95
Author(s) -
Kovács Bertalan,
ZajáczEpresi Nóra,
Gáspári Zoltán
Publication year - 2020
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13626
Subject(s) - pdz domain , postsynaptic density , biophysics , chemistry , ligand (biochemistry) , postsynaptic potential , plasma protein binding , molecular dynamics , crystallography , biochemistry , biology , receptor , computational chemistry
The postsynaptic density protein‐95 (PSD‐95) regulates synaptic plasticity through interactions mediated by its peptide‐binding PDZ domains. The two N‐terminal PDZ domains of PSD‐95 form an autonomous structural unit, and their interdomain orientation and dynamics depend on ligand binding. To understand the mechanistic details of the effect of ligand binding, we generated conformational ensembles using available experimentally determined nuclear Overhauser effect interatomic distances and S 2 order parameters. In our approach, the fast dynamics of the two domains is treated independently. We find that intradomain structural changes induced by ligand binding modulate 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, which influences both intradomain motions and supramodular rearrangement.