Forkhead Domains of FOXO Transcription Factors Differ in both Overall Conformation and Dynamics

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F19%3A00510048" target="_blank" >RIV/61388963:_____/19:00510048 - isvavai.cz</a>

Alternative codes found

RIV/67985823:_____/19:00510048 RIV/00216208:11310/19:10403407

Result on the web

<a href="https://doi.org/10.3390/cells8090966" target="_blank" >https://doi.org/10.3390/cells8090966</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/cells8090966" target="_blank" >10.3390/cells8090966</a>

Result language

angličtina

Original language name

Forkhead Domains of FOXO Transcription Factors Differ in both Overall Conformation and Dynamics

Original language description

FOXO transcription factors regulate cellular homeostasis, longevity and response to stress. FOXO1 (also known as FKHR) is a key regulator of hepatic glucose production and lipid metabolism, and its specific inhibition may have beneficial effects on diabetic hyperglycemia by reducing hepatic glucose production. Moreover, all FOXO proteins are considered potential drug targets for drug resistance prevention in cancer therapy. However, the development of specific FOXO inhibitors requires a detailed understanding of structural differences between individual FOXO DNA-binding domains. The high-resolution structure of the DNA-binding domain of FOXO1 reported in this study and its comparison with structures of other FOXO proteins revealed differences in both their conformation and flexibility. These differences are encoded by variations in protein sequences and account for the distinct functions of FOXO proteins. In particular, the positions of the helices H1, H2 and H3, whose interface form the hydrophobic core of the Forkhead domain, and the interactions between hydrophobic residues located on the interface between the N-terminal segment, the H2-H3 loop, and the recognition helix H3 differ among apo FOXO1, FOXO3 and FOXO4 proteins. Therefore, the availability of apo structures of DNA-binding domains of all three major FOXO proteins will support the development of FOXO-type-specific inhibitors.

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)

Publication year

2019

Confidentiality

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

Name of the periodical

Cells

ISSN

2073-4409

e-ISSN

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Volume of the periodical

8

Issue of the periodical within the volume

9

Country of publishing house

CH - SWITZERLAND

Number of pages

14

Pages from-to

966

UT code for WoS article

000489103800025

EID of the result in the Scopus database

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