Overlapping but distinct: a new model for G-quadruplex biochemical specificity

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F21%3A00541403" target="_blank" >RIV/61388963:_____/21:00541403 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11320/21:10428492 RIV/00216208:11310/21:10428492

Result on the web

<a href="https://doi.org/10.1093/nar/gkab037" target="_blank" >https://doi.org/10.1093/nar/gkab037</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/nar/gkab037" target="_blank" >10.1093/nar/gkab037</a>

Result language

angličtina

Original language name

Overlapping but distinct: a new model for G-quadruplex biochemical specificity

Original language description

G-quadruplexes are noncanonical nucleic acid structures formed by stacked guanine tetrads. They are capable of a range of functions and thought to play widespread biological roles. This diversity raises an important question: what determines the biochemical specificity of G-quadruplex structures? The answer is particularly important from the perspective of biological regulation because genomes can contain hundreds of thousands of G-quadruplexes with a range of functions. Here we analyze the specificity of each sequence in a 496-member library of variants of a reference G-quadruplex with respect to five functions. Our analysis shows that the sequence requirements of G-quadruplexes with these functions are different from one another, with some mutations altering biochemical specificity by orders of magnitude. Mutations in tetrads have larger effects than mutations in loops, and changes in specificity are correlated with changes in multimeric state. To complement our biochemical data we determined the solution structure of a monomeric G-quadruplex from the library. The stacked and accessible tetrads rationalize why monomers tend to promote a model peroxidase reaction and generate fluorescence. Our experiments support a model in which the sequence requirements of G-quadruplexes with different functions are overlapping but distinct. This has implications for biological regulation, bioinformatics, and drug design.

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

<a href="/en/project/EF16_019%2F0000729" target="_blank" >EF16_019/0000729: Chemical biology for drugging undruggable targets</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2021

Confidentiality

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

Name of the periodical

Nucleic Acids Research

ISSN

0305-1048

e-ISSN

1362-4962

Volume of the periodical

49

Issue of the periodical within the volume

4

Country of publishing house

GB - UNITED KINGDOM

Number of pages

12

Pages from-to

1816-1827

UT code for WoS article

000637321900008

EID of the result in the Scopus database

2-s2.0-85102410684