A class III ligand oscillates between internal and terminal binding modes as it engages with the Dishevelled PDZ domain
The result's identifiers
Result code in 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>
Alternative codes found
RIV/00216224:14740/25:00142910
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
A class III ligand oscillates between internal and terminal binding modes as it engages with the Dishevelled PDZ domain
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10610 - Biophysics
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Structure
ISSN
0969-2126
e-ISSN
1878-4186
Volume of the periodical
33
Issue of the periodical within the volume
8
Country of publishing house
US - UNITED STATES
Number of pages
18
Pages from-to
1362-1373
UT code for WoS article
001585536400008
EID of the result in the Scopus database
2-s2.0-105008036078