Počet záznamů: 1

14-3-3 proteins inactivate DAPK2 by promoting its dimerization and protecting key regulatory phosphosites

SYSNO ASEP	0545402
Druh ASEP	J - Článek v odborném periodiku
Zařazení RIV	J - Článek v odborném periodiku
Poddruh J	Článek ve WOS
Název	14-3-3 proteins inactivate DAPK2 by promoting its dimerization and protecting key regulatory phosphosites
Tvůrce(i)	Horváth, Matej (FGU-C)_ORCID Petrvalská, Olivia (FGU-C)_{RID, ORCID, SAI} Herman, P. (CZ) Obšilová, Veronika (FGU-C)_{RID, ORCID, SAI} Obšil, Tomáš (FGU-C)_{RID, ORCID}
Číslo článku	986
Zdroj.dok.	Communications Biology. - : Nature Publishing Group Roč. 4, č. 1 (2021)
Poč.str.	14 s.
Jazyk dok.	eng - angličtina
Země vyd.	GB - Velká Británie
Klíč. slova	protein structure and function ; protein kinase ; DAPK ; 14-3-3 protein ; apoptosis ; phosphorylation
Vědní obor RIV	CE - Biochemie
Obor OECD	Biochemistry and molecular biology
CEP	GA19-00121S GA ČR - Grantová agentura ČR
Výzkumná infrastruktura	CIISB II - 90127 - Masarykova univerzita
Způsob publikování	Open access
Institucionální podpora	FGU-C - RVO:67985823
UT WOS	000686777300004
EID SCOPUS	85113253261
DOI	10.1038/s42003-021-02518-y
Anotace	Death-associated protein kinase 2 (DAPK2) is a CaM-regulated Ser/Thr protein kinase, involved in apoptosis, autophagy, granulocyte differentiation and motility regulation, whose activity is controlled by autoinhibition, autophosphorylation, dimerization and interaction with scaffolding proteins 14-3-3. However, the structural basis of 14-3-3-mediated DAPK2 regulation remains unclear. Here, we structurally and biochemically characterize the full-length human DAPK2:14-3-3 complex by combining several biophysical techniques. The results from our X-ray crystallographic analysis revealed that Thr369 phosphorylation at the DAPK2 C terminus creates a high-affinity canonical mode III 14-3-3-binding motif, further enhanced by the diterpene glycoside Fusicoccin A. Moreover, concentration-dependent DAPK2 dimerization is disrupted by Ca2+/CaM binding and stabilized by 14-3-3 binding in solution, thereby protecting the DAPK2 inhibitory autophosphorylation site Ser318 against dephosphorylation and preventing Ca2+/CaM binding. Overall, our findings provide mechanistic insights into 14-3-3-mediated DAPK2 inhibition and highlight the potential of the DAPK2:14-3-3 complex as a target for anti‐inflammatory therapies.
Pracoviště	Fyziologický ústav
Kontakt	Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400
Rok sběru	2022
Elektronická adresa	https://doi.org/10.1038/s42003-021-02518-y

Počet záznamů: 1