MS-Based Approaches Enable the Structural Characterization of Transcription Factor/DNA Response Element Complex

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F19%3A00519095" target="_blank" >RIV/61388971:_____/19:00519095 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11310/19:10402753

Result on the web

<a href="https://www.mdpi.com/2218-273X/9/10/535" target="_blank" >https://www.mdpi.com/2218-273X/9/10/535</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/biom9100535" target="_blank" >10.3390/biom9100535</a>

Result language

angličtina

Original language name

MS-Based Approaches Enable the Structural Characterization of Transcription Factor/DNA Response Element Complex

Original language description

The limited information available on the structure of complexes involving transcription factors and cognate DNA response elements represents a major obstacle in the quest to understand their mechanism of action at the molecular level. We implemented a concerted structural proteomics approach, which combined hydrogen-deuterium exchange (HDX), quantitative protein-protein and protein-nucleic acid cross-linking (XL), and homology analysis, to model the structure of the complex between the full-length DNA binding domain (DBD) of Forkhead box protein O4 (FOXO4) and its DNA binding element (DBE). The results confirmed that FOXO4-DBD assumes the characteristic forkhead topology shared by these types of transcription factors, but its binding mode differs significantly from those of other members of the family. The results showed that the binding interaction stabilized regions that were rather flexible and disordered in the unbound form. Surprisingly, the conformational effects were not limited only to the interface between bound components, but extended also to distal regions that may be essential to recruiting additional factors to the transcription machinery. In addition to providing valuable new insights into the binding mechanism, this project provided an excellent evaluation of the merits of structural proteomics approaches in the investigation of systems that are not directly amenable to traditional high-resolution techniques.

Czech name

—

Czech description

—

Type

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

CEP classification

—

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

Biomolecules

ISSN

2218-273X

e-ISSN

—

Volume of the periodical

9

Issue of the periodical within the volume

10

Country of publishing house

CH - SWITZERLAND

Number of pages

21

Pages from-to

535

UT code for WoS article

000497726800027

EID of the result in the Scopus database

2-s2.0-85072692405