Structural basis of binding the unique N-terminal domain of
microtubule-associated protein 2c to proteins regulating
kinases of signaling pathways.

J 2024

Structural basis of binding the unique N-terminal domain of microtubule-associated protein 2c to proteins regulating kinases of signaling pathways.

BARTOŠÍK, Viktor, Jitka PLUCAROVÁ, Alice LANÍKOVÁ, Zuzana JANÁČKOVÁ, Petr PADRTA et. al.

Základní údaje

Originální název

Structural basis of binding the unique N-terminal domain of microtubule-associated protein 2c to proteins regulating kinases of signaling pathways.

Autoři

BARTOŠÍK, Viktor, Jitka PLUCAROVÁ, Alice LANÍKOVÁ, Zuzana JANÁČKOVÁ, Petr PADRTA, Séverine JANSEN, Vojtěch VAŘEČKA, Tobias GRUBER, Stephan M. FELLER a Lukáš ŽÍDEK

Vydání

International Journal of Biological Chemistry, ANSInet, 2024, 1819-155X

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10700 1.7 Other natural sciences

Stát vydavatele

Nizozemské království

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.1016/j.jbc.2024.107551

Klíčová slova anglicky

A-kinase anchoring protein (AKAP); growth factor receptor-bound protein 2 (GRB2); microtubule associated protein (MAP) 2; nuclear magnetic resonance (NMR); protein kinase A (PKA)

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 1. 10. 2024 17:40, Mgr. Viktor Bartošík

Anotace

V originále

Isoforms of microtubule-associated protein 2 (MAP2) differ from their homolog Tau in the sequence and interactions of the N-terminal region. Binding of the N-terminal region of MAP2c (N-MAP2c) to the dimerization/docking domains of the regulatory subunit RIIα of cAMP-dependent protein kinase (RIIDD2) and to the Src-homology domain 2 (SH2) of growth factor receptor-bound protein 2 (Grb2) have been described long time ago. However, the structural features of the complexes remained unknown due to the disordered nature of MAP2. Here, we provide structural description of the complexes. We have solved solution structure of N-MAP2c in complex with RIIDD2, confirming formation of an amphiphilic α-helix of MAP2c upon binding, defining orientation of the α-helix in the complex and showing that its binding register differs from previous predictions. Using chemical shift mapping, we characterized the binding interface of SH2-Grb2 and rat MAP2c phosphorylated by the tyrosine kinase Fyn in their complex and proposed a model explaining differences between SH2-Grb2 complexes with rat MAP2c and phosphopeptides with a Grb2-specific sequence. The results provide the structural basis of a potential role of MAP2 in regulating cAMP-dependent phosphorylation cascade via interactions with RIIDD2 and Ras signaling pathway via interactions with SH2-Grb2.

Návaznosti

CZ.02.1.01/0.0/0.0/18_046/0015974, velká výzkumná infrastruktura
(Kód CEP: EF18_046/0015974)

Název: Modernizace České infrastruktury pro integrativní strukturní biologii (Akronym: UP CIISB)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Modernizace České infrastruktury pro integrativní strukturní biologii, PO 1 Posilování kapacit pro kvalitní výzkum

GA20-12669S, projekt VaV

Název: Interakce určující fyziologické funkce proteinu Microtubule Associated Protein 2c s atomovým rozlišením

Investor: Grantová agentura ČR, Interactions defining physiological functions of Microtubule Associated Protein 2c at atomic resolution

LM2023042, projekt VaV

Název: Česká infrastruktura pro integrativní strukturní biologii

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CIISB - Česká infrastruktura pro integrativní strukturní biologii

Citovat

BARTOŠÍK, Viktor, Jitka PLUCAROVÁ, Alice LANÍKOVÁ, Zuzana JANÁČKOVÁ, Petr PADRTA, Séverine JANSEN, Vojtěch VAŘEČKA, Tobias GRUBER, Stephan M. FELLER a Lukáš ŽÍDEK. Structural basis of binding the unique N-terminal domain of microtubule-associated protein 2c to proteins regulating kinases of signaling pathways. International Journal of Biological Chemistry. ANSInet, 2024, roč. 300, č. 8. ISSN 1819-155X. Dostupné z: https://dx.doi.org/10.1016/j.jbc.2024.107551.

@article{2439297,
   author = {Bartošík, Viktor and Plucarová, Jitka and Laníková, Alice and Janáčková, Zuzana and Padrta, Petr and Jansen, Séverine and Vařečka, Vojtěch and Gruber, Tobias and Feller, Stephan M. and Žídek, Lukáš},
   article_number = {8},
   doi = {http://dx.doi.org/10.1016/j.jbc.2024.107551},
   keywords = {A-kinase anchoring protein (AKAP); growth factor receptor-bound protein 2 (GRB2); microtubule associated protein (MAP) 2; nuclear magnetic resonance (NMR); protein kinase A (PKA)},
   language = {eng},
   issn = {1819-155X},
   journal = {International Journal of Biological Chemistry},
   title = {Structural basis of binding the unique N-terminal domain of microtubule-associated protein 2c to proteins regulating kinases of signaling pathways.},
   url = {https://www.sciencedirect.com/science/article/pii/S0021925824020520?via%3Dihub},
   volume = {300},
   year = {2024}
}

TY  - JOUR
ID  - 2439297
AU  - Bartošík, Viktor - Plucarová, Jitka - Laníková, Alice - Janáčková, Zuzana - Padrta, Petr - Jansen, Séverine - Vařečka, Vojtěch - Gruber, Tobias - Feller, Stephan M. - Žídek, Lukáš
PY  - 2024
TI  - Structural basis of binding the unique N-terminal domain of microtubule-associated protein 2c to proteins regulating kinases of signaling pathways.
JF  - International Journal of Biological Chemistry
VL  - 300
IS  - 8
PB  - ANSInet
SN  - 1819155X
KW  - A-kinase anchoring protein (AKAP)
KW  - growth factor receptor-bound protein 2 (GRB2)
KW  - microtubule associated protein (MAP) 2
KW  - nuclear magnetic resonance (NMR)
KW  - protein kinase A (PKA)
UR  - https://www.sciencedirect.com/science/article/pii/S0021925824020520?via%3Dihub
N2  - Isoforms of microtubule-associated protein 2 (MAP2) differ from their homolog Tau in the sequence and interactions of the N-terminal region. Binding of the N-terminal region of MAP2c (N-MAP2c) to the dimerization/docking domains of the regulatory subunit RIIα of cAMP-dependent protein kinase (RIIDD2) and to the Src-homology domain 2 (SH2) of growth factor receptor-bound protein 2 (Grb2) have been described long time ago. However, the structural features of the complexes remained unknown due to the disordered nature of MAP2. Here, we provide structural description of the complexes. We have solved solution structure of N-MAP2c in complex with RIIDD2, confirming formation of an amphiphilic α-helix of MAP2c upon binding, defining orientation of the α-helix in the complex and showing that its binding register differs from previous predictions. Using chemical shift mapping, we characterized the binding interface of SH2-Grb2 and rat MAP2c phosphorylated by the tyrosine kinase Fyn in their complex and proposed a model explaining differences between SH2-Grb2 complexes with rat MAP2c and phosphopeptides with a Grb2-specific sequence. The results provide the structural basis of a potential role of MAP2 in regulating cAMP-dependent phosphorylation cascade via interactions with RIIDD2 and Ras signaling pathway via interactions with SH2-Grb2.
ER  -

BARTOŠÍK, Viktor, Jitka PLUCAROVÁ, Alice LANÍKOVÁ, Zuzana JANÁČKOVÁ, Petr PADRTA, Séverine JANSEN, Vojtěch VAŘEČKA, Tobias GRUBER, Stephan M. FELLER a Lukáš ŽÍDEK. Structural basis of binding the unique N-terminal domain of microtubule-associated protein 2c to proteins regulating kinases of signaling pathways. \textit{International Journal of Biological Chemistry}. ANSInet, 2024, roč.~300, č.~8. ISSN~1819-155X. Dostupné z: https://dx.doi.org/10.1016/j.jbc.2024.107551.

Podrobný výpis o publikaci