J 2021

Phosphorylation-induced changes in the PDZ domain of Dishevelled 3

JURÁSEK, Miroslav, Jitender KUMAR, Petra PACLÍKOVÁ, Alka Kumari JADAUN, Konstantinos TRIPSIANES et. al.

Basic information

Original name

Phosphorylation-induced changes in the PDZ domain of Dishevelled 3

Authors

JURÁSEK, Miroslav (203 Czech Republic, belonging to the institution), Jitender KUMAR (356 India, belonging to the institution), Petra PACLÍKOVÁ (203 Czech Republic, belonging to the institution), Alka Kumari JADAUN (356 India, belonging to the institution), Konstantinos TRIPSIANES (300 Greece, belonging to the institution), Vítězslav BRYJA (203 Czech Republic, belonging to the institution) and Robert VÁCHA (203 Czech Republic, belonging to the institution)

Edition

Scientific Reports, NATURE PUBLISHING GROUP, 2021, 2045-2322

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

Germany

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 4.996

RIV identification code

RIV/00216224:14740/21:00118888

Organization unit

Central European Institute of Technology

DOI

UT WoS

000609782400005

Keywords in English

HUMAN PHOSPHATASE HPTP1E; PARTICLE MESH EWALD; PROTEIN INTERACTIONS; LIGAND RECOGNITION; PAR-6 PDZ; BINDING; DYNAMICS; REVEALS; COMPLEX; MODES

Tags

Tags

International impact, Reviewed
Změněno: 27/10/2024 15:17, Ing. Martina Blahová

Abstract

V originále

The PDZ domain of Dishevelled 3 protein belongs to a highly abundant protein recognition motif which typically binds short C-terminal peptides. The affinity of the PDZ towards the peptides could be fine-tuned by a variety of post-translation modifications including phosphorylation. However, how phosphorylations affect the PDZ structure and its interactions with ligands remains elusive. Combining molecular dynamics simulations, NMR titration, and biological experiments, we explored the role of previously reported phosphorylation sites and their mimetics in the Dishevelled PDZ domain. Our observations suggest three major roles for phosphorylations: (1) acting as an on/off PDZ binding switch, (2) allosterically affecting the binding groove, and (3) influencing the secondary binding site. Our simulations indicated that mimetics had similar but weaker effects, and the effects of distinct sites were non-additive. This study provides insight into the Dishevelled regulation by PDZ phosphorylation. Furthermore, the observed effects could be used to elucidate the regulation mechanisms in other PDZ domains.

Links

GA17-11571S, research and development project
Name: Amfifilní peptidy na fosfolipidových membránách
Investor: Czech Science Foundation
GA18-17658S, research and development project
Name: Odhalení tajemství signální dráhy WNT analýzou struktury proteinu Dishevelled
Investor: Czech Science Foundation
LM2015085, research and development project
Name: CERIT Scientific Cloud (Acronym: CERIT-SC)
Investor: Ministry of Education, Youth and Sports of the CR, CERIT Scientific Cloud
LQ1601, research and development project
Name: CEITEC 2020 (Acronym: CEITEC2020)
Investor: Ministry of Education, Youth and Sports of the CR
MUNI/G/0739/2017, interní kód MU
Name: Pushing the limits in automated NMR structure determination using a single 4D NOESY spectrum and machine learning methods
Investor: Masaryk University, INTERDISCIPLINARY - Interdisciplinary research projects
MUNI/G/1100/2016, interní kód MU
Name: Computational chemistry for Wnt signaling pathway
Investor: Masaryk University, INTERDISCIPLINARY - Interdisciplinary research projects
90042, large research infrastructures
Name: CESNET II
90043, large research infrastructures
Name: CIISB
90070, large research infrastructures
Name: IT4Innovations
90127, large research infrastructures
Name: CIISB II