A class III ligand oscillates between internal and terminal binding modes as it engages with the Dishevelled PDZ domain

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F25%3A00646518" target="_blank" >RIV/86652036:_____/25:00646518 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14740/25:00142910

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S096921262500190X" target="_blank" >https://www.sciencedirect.com/science/article/pii/S096921262500190X</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.str.2025.05.012" target="_blank" >10.1016/j.str.2025.05.012</a>

Jazyk výsledku

angličtina

Název v původním jazyce

A class III ligand oscillates between internal and terminal binding modes as it engages with the Dishevelled PDZ domain

Popis výsledku v původním jazyce

One of the largest domain-motif interactomes in human involves PSD-95/Discs-large/ZO-1 (PDZ) domains. The framework for understanding the PDZ interactome is well established. However the functional dynamics associated with PDZ-ligand interactions are poorly understood. Here, we report a dual PDZ-binding mode that ascribes unique dynamic features to class III ligand recognition. The crystal structure revealed that the PDZ domain can recognize either of the carboxylate moieties (terminal or internal) present in the class III ligand and laid out the register rules responsible for the dual recognition. Variants of the ligand designed to retain one or the other carboxylate of the native sequence were sufficient for PDZ binding. The conformational dynamics of PDZ probed by NMR relaxation dispersion experiments demonstrated that the class III ligand is shuffling binding modes as it engages with the PDZ domain. Our mechanistic findings reveal yet another aspect of PDZ binding plasticity specific to class III ligands.

Název v anglickém jazyce

A class III ligand oscillates between internal and terminal binding modes as it engages with the Dishevelled PDZ domain

Popis výsledku anglicky

One of the largest domain-motif interactomes in human involves PSD-95/Discs-large/ZO-1 (PDZ) domains. The framework for understanding the PDZ interactome is well established. However the functional dynamics associated with PDZ-ligand interactions are poorly understood. Here, we report a dual PDZ-binding mode that ascribes unique dynamic features to class III ligand recognition. The crystal structure revealed that the PDZ domain can recognize either of the carboxylate moieties (terminal or internal) present in the class III ligand and laid out the register rules responsible for the dual recognition. Variants of the ligand designed to retain one or the other carboxylate of the native sequence were sufficient for PDZ binding. The conformational dynamics of PDZ probed by NMR relaxation dispersion experiments demonstrated that the class III ligand is shuffling binding modes as it engages with the PDZ domain. Our mechanistic findings reveal yet another aspect of PDZ binding plasticity specific to class III ligands.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10610 - Biophysics

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Structure

ISSN

0969-2126

e-ISSN

1878-4186

Svazek periodika

33

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

18

Strana od-do

1362-1373

Kód UT WoS článku

001585536400008

EID výsledku v databázi Scopus

2-s2.0-105008036078