Carboxy-terminal polyglutamylation regulates signaling and phase separation of the Dishevelled protein

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F24%3A00604464" target="_blank" >RIV/86652036:_____/24:00604464 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14310/24:00137753 RIV/00216208:11310/24:10495183

Výsledek na webu

<a href="https://www.embopress.org/doi/full/10.1038/s44318-024-00254-7" target="_blank" >https://www.embopress.org/doi/full/10.1038/s44318-024-00254-7</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s44318-024-00254-7" target="_blank" >10.1038/s44318-024-00254-7</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Carboxy-terminal polyglutamylation regulates signaling and phase separation of the Dishevelled protein

Popis výsledku v původním jazyce

Polyglutamylation is a reversible posttranslational modification that is catalyzed by enzymes of the tubulin tyrosine ligase-like (TTLL) family. Here, we found that TTLL11 generates a previously unknown type of polyglutamylation that is initiated by the addition of a glutamate residue to the free C-terminal carboxyl group of a substrate protein. TTLL11 efficiently polyglutamylates the Wnt signaling protein Dishevelled 3 (DVL3), thereby changing the interactome of DVL3. Polyglutamylation increases the capacity of DVL3 to get phosphorylated, to undergo phase separation, and to act in the noncanonical Wnt pathway. Both carboxy-terminal polyglutamylation and the resulting reduction in phase separation capacity of DVL3 can be reverted by the deglutamylating enzyme CCP6, demonstrating a causal relationship between TTLL11-mediated polyglutamylation and phase separation. Thus, C-terminal polyglutamylation represents a new type of posttranslational modification, broadening the range of proteins that can be modified by polyglutamylation and providing the first evidence that polyglutamylation can modulate protein phase separation.

Název v anglickém jazyce

Carboxy-terminal polyglutamylation regulates signaling and phase separation of the Dishevelled protein

Popis výsledku anglicky

Polyglutamylation is a reversible posttranslational modification that is catalyzed by enzymes of the tubulin tyrosine ligase-like (TTLL) family. Here, we found that TTLL11 generates a previously unknown type of polyglutamylation that is initiated by the addition of a glutamate residue to the free C-terminal carboxyl group of a substrate protein. TTLL11 efficiently polyglutamylates the Wnt signaling protein Dishevelled 3 (DVL3), thereby changing the interactome of DVL3. Polyglutamylation increases the capacity of DVL3 to get phosphorylated, to undergo phase separation, and to act in the noncanonical Wnt pathway. Both carboxy-terminal polyglutamylation and the resulting reduction in phase separation capacity of DVL3 can be reverted by the deglutamylating enzyme CCP6, demonstrating a causal relationship between TTLL11-mediated polyglutamylation and phase separation. Thus, C-terminal polyglutamylation represents a new type of posttranslational modification, broadening the range of proteins that can be modified by polyglutamylation and providing the first evidence that polyglutamylation can modulate protein phase separation.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

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

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

EMBO Journal

ISSN

0261-4189

e-ISSN

1460-2075

Svazek periodika

43

Číslo periodika v rámci svazku

22

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

32

Strana od-do

5635-5666

Kód UT WoS článku

001322467100003

EID výsledku v databázi Scopus

2-s2.0-85205365599