14-3-3 protein binding blocks the dimerization interface of
caspase-2

J 2020

14-3-3 protein binding blocks the dimerization interface of caspase-2

KALABOVA, Dana; Frantisek FILANDR; Miroslava ALBLOVA; Olivia PETRVALSKA; Matej HORVATH et al.

Základní údaje

Originální název

14-3-3 protein binding blocks the dimerization interface of caspase-2

Autoři

KALABOVA, Dana; Frantisek FILANDR; Miroslava ALBLOVA; Olivia PETRVALSKA; Matej HORVATH; Petr MAN; Tomas OBSIL a Veronika OBSILOVA

Vydání

FEBS Journal, MALDEN, Blackwell, 2020, 1742-464X

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 5.542

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:90043/20:00139206

Organizační jednotka

CIISB

Klíčová slova anglicky

14-3-3 protein; caspase-2; crystallography; H; D exchange; protein-protein interaction

Štítky

ne MU, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 28. 3. 2025 17:22, Mgr. Eva Dubská

Anotace

V originále

Among all species, caspase-2 (C2) is the most evolutionarily conserved caspase required for effective initiation of apoptosis following death stimuli. C2 is activated through dimerization and autoproteolytic cleavage and inhibited through phosphorylation at Ser(139) and Ser(164), within the linker between the caspase recruitment and p19 domains of the zymogen, followed by association with the adaptor protein 14-3-3, which maintains C2 in its immature form procaspase (proC2). However, the mechanism of 14-3-3-dependent inhibition of C2 activation remains unclear. Here, we report the structural characterization of the complex between proC2 and 14-3-3 by hydrogen/deuterium mass spectrometry and protein crystallography to determine the molecular basis for 14-3-3-mediated inhibition of C2 activation. Our data reveal that the 14-3-3 dimer interacts with proC2 not only through ligand-binding grooves but also through other regions outside the central channel, thus explaining the isoform-dependent specificity of 14-3-3 protein binding to proC2 and the substantially higher binding affinity of 14-3-3 protein to proC2 than to the doubly phosphorylated peptide. The formation of the complex between 14-3-3 protein and proC2 does not induce any large conformational change in proC2. Furthermore, 14-3-3 protein interacts with and masks both the nuclear localization sequence and the C-terminal region of the p12 domain of proC2 through transient interactions in which both the p19 and p12 domains of proC2 are not firmly docked onto the surface of 14-3-3. This masked region of p12 domain is involved in C2 dimerization. Therefore, 14-3-3 protein likely inhibits proC2 activation by blocking its dimerization surface.

Návaznosti

90043, velká výzkumná infrastruktura

Název: CIISB

Citovat

KALABOVA, Dana; Frantisek FILANDR; Miroslava ALBLOVA; Olivia PETRVALSKA; Matej HORVATH; Petr MAN; Tomas OBSIL a Veronika OBSILOVA. 14-3-3 protein binding blocks the dimerization interface of caspase-2. FEBS Journal. MALDEN: Blackwell, 2020, roč. 287, č. 16, s. 3494-3510. ISSN 1742-464X. Dostupné z: https://doi.org/10.1111/febs.15215.

@article{2487291,
   author = {Kalabova, Dana and Filandr, Frantisek and Alblova, Miroslava and Petrvalska, Olivia and Horvath, Matej and Man, Petr and Obsil, Tomas and Obsilova, Veronika},
   article_location = {MALDEN},
   article_number = {16},
   doi = {https://doi.org/10.1111/febs.15215},
   keywords = {14-3-3 protein; caspase-2; crystallography; H; D exchange; protein-protein interaction},
   language = {eng},
   issn = {1742-464X},
   journal = {FEBS Journal},
   title = {14-3-3 protein binding blocks the dimerization interface of caspase-2},
   url = {https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.15215},
   volume = {287},
   year = {2020}
}

TY  - JOUR
ID  - 2487291
AU  - Kalabova, Dana - Filandr, Frantisek - Alblova, Miroslava - Petrvalska, Olivia - Horvath, Matej - Man, Petr - Obsil, Tomas - Obsilova, Veronika
PY  - 2020
TI  - 14-3-3 protein binding blocks the dimerization interface of caspase-2
JF  - FEBS Journal
VL  - 287
IS  - 16
SP  - 3494-3510
EP  - 3494-3510
PB  - Blackwell
SN  - 1742464X
KW  - 14-3-3 protein
KW  - caspase-2
KW  - crystallography
KW  - H
KW  - D exchange
KW  - protein-protein interaction
UR  - https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.15215
N2  - Among all species, caspase-2 (C2) is the most evolutionarily conserved caspase required for effective initiation of apoptosis following death stimuli. C2 is activated through dimerization and autoproteolytic cleavage and inhibited through phosphorylation at Ser(139) and Ser(164), within the linker between the caspase recruitment and p19 domains of the zymogen, followed by association with the adaptor protein 14-3-3, which maintains C2 in its immature form procaspase (proC2). However, the mechanism of 14-3-3-dependent inhibition of C2 activation remains unclear. Here, we report the structural characterization of the complex between proC2 and 14-3-3 by hydrogen/deuterium mass spectrometry and protein crystallography to determine the molecular basis for 14-3-3-mediated inhibition of C2 activation. Our data reveal that the 14-3-3 dimer interacts with proC2 not only through ligand-binding grooves but also through other regions outside the central channel, thus explaining the isoform-dependent specificity of 14-3-3 protein binding to proC2 and the substantially higher binding affinity of 14-3-3 protein to proC2 than to the doubly phosphorylated peptide. The formation of the complex between 14-3-3 protein and proC2 does not induce any large conformational change in proC2. Furthermore, 14-3-3 protein interacts with and masks both the nuclear localization sequence and the C-terminal region of the p12 domain of proC2 through transient interactions in which both the p19 and p12 domains of proC2 are not firmly docked onto the surface of 14-3-3. This masked region of p12 domain is involved in C2 dimerization. Therefore, 14-3-3 protein likely inhibits proC2 activation by blocking its dimerization surface.
ER  -

KALABOVA, Dana; Frantisek FILANDR; Miroslava ALBLOVA; Olivia PETRVALSKA; Matej HORVATH; Petr MAN; Tomas OBSIL a Veronika OBSILOVA. 14-3-3 protein binding blocks the dimerization interface of caspase-2. \textit{FEBS Journal}. MALDEN: Blackwell, 2020, roč.~287, č.~16, s.~3494-3510. ISSN~1742-464X. Dostupné z: https://doi.org/10.1111/febs.15215.

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