CaMKK2 kinase domain interacts with the autoinhibitory region through the N-terminal lobe including the RP insert

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F18%3A10386123" target="_blank" >RIV/00216208:11310/18:10386123 - isvavai.cz</a>

Alternative codes found

RIV/67985823:_____/18:00495290 RIV/00216208:11320/18:10386123

Result on the web

<a href="https://doi.org/10.1016/j.bbagen.2018.07.025" target="_blank" >https://doi.org/10.1016/j.bbagen.2018.07.025</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bbagen.2018.07.025" target="_blank" >10.1016/j.bbagen.2018.07.025</a>

Result language

angličtina

Original language name

CaMKK2 kinase domain interacts with the autoinhibitory region through the N-terminal lobe including the RP insert

Original language description

Background: Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2), a member of the Ca2+/calmodulin-dependent kinase (CaMK) family, functions as an upstream activator of CaMKI, CaMKIV and AMP activated protein kinase. Thus, CaMKK2 is involved in the regulation of several key physiological and pathophysiological processes. Previous studies have suggested that Ca2+/CaM binding may cause unique conformational changes in the CaMKKs compared with other CaMKs. However, the underlying mechanistic details remain unclear. Methods: In this study, hydrogen-deuterium exchange coupled to mass spectrometry, time-resolved fluorescence spectroscopy, small-angle x-ray scattering and chemical cross-linking were used to characterize Ca2+/CaM binding-induced structural changes in CaMKK2. Results: Our data suggest that: (i) the CaMKK2 kinase domain interacts with the autoinhibitory region (AID) through the N-terminal lobe of the kinase domain including the RP insert, a segment important for targeting downstream substrate kinases; (ii) Ca2+/CaM binding affects the structure of several regions surrounding the ATP-binding pocket, including the activation segment; (iii) although the CaMKK2:Ca2+/CaM complex shows high conformational flexibility, most of its molecules are rather compact; and (iv) AID-bound Ca2+/CaM transiently interacts with the CaMKK2 kinase domain. Conclusions: Interactions between the CaMKK2 kinase domain and the AID differ from those of other CaMKs. In the absence of Ca2+/CaM binding the autoinhibitory region inhibits CaMKK2 by both blocking access to the RP insert and by affecting the structure of the ATP-binding pocket. General significance: Our results corroborate the hypothesis that Ca2+/CaM binding causes unique conformational changes in the CaMKKs relative to other CaMKs.

Czech name

—

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

—

OECD FORD branch

10403 - Physical chemistry

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)

Publication year

2018

Confidentiality

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

Name of the periodical

Biochimica et Biophysica Acta - General Subjects

ISSN

0304-4165

e-ISSN

—

Volume of the periodical

1862

Issue of the periodical within the volume

10

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

10

Pages from-to

2304-2313

UT code for WoS article

000443665300020

EID of the result in the Scopus database

2-s2.0-85050768718