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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F24%3A00138072" target="_blank" >RIV/00216224:14740/24:00138072 - isvavai.cz</a>

Result on the web

<a href="https://www.jbc.org/article/S0021-9258(24)02052-0/fulltext" target="_blank" >https://www.jbc.org/article/S0021-9258(24)02052-0/fulltext</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jbc.2024.107551" target="_blank" >10.1016/j.jbc.2024.107551</a>

Result language

angličtina

Original language name

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

Original language description

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 RIIa 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 a-helix of MAP2c upon binding, defining orientation of the ahelix 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 cAMPdependent phosphorylation cascade via interactions with RIIDD2 and Ras signaling pathway via interactions with SH2

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach

Publication year

2024

Confidentiality

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

Name of the periodical

International Journal of Biological Chemistry

ISSN

0021-9258

e-ISSN

1083-351X

Volume of the periodical

300

Issue of the periodical within the volume

8

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

22

Pages from-to

1-22

UT code for WoS article

001365739800001

EID of the result in the Scopus database

2-s2.0-85200983503