Unique peptidic agonists of a juvenile hormone receptor with species-specific effects on insect development and reproduction

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F22%3A00564793" target="_blank" >RIV/60077344:_____/22:00564793 - isvavai.cz</a>

Alternative codes found

RIV/68378050:_____/22:00564793 RIV/61388963:_____/22:00564793 RIV/60076658:12310/22:43905983

Result on the web

<a href="https://www.pnas.org/doi/epdf/10.1073/pnas.2215541119" target="_blank" >https://www.pnas.org/doi/epdf/10.1073/pnas.2215541119</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1073/pnas.2215541119" target="_blank" >10.1073/pnas.2215541119</a>

Result language

angličtina

Original language name

Unique peptidic agonists of a juvenile hormone receptor with species-specific effects on insect development and reproduction

Original language description

Juvenile hormones (JHs) control insect metamorphosis and reproduction. JHs act through a receptor complex consisting of methoprene-tolerant (Met) and taiman (Tai) proteins to induce transcription of specific genes. Among chemically diverse synthetic JH mimics (juvenoids), some of which serve as insecticides, unique peptidic juvenoids stand out as being highly potent yet exquisitely selective to a specific family of true bugs. Their mode of action is unknown. Here we demonstrate that, like established JH receptor agonists, peptidic juvenoids act upon the JHR Met to halt metamorphosis in larvae of the linden bug, Pyrrhocoris apterus. Peptidic juvenoids induced ligand-dependent dimerization between Met and Tai proteins from P. apterus but, consistent with their selectivity, not from other insects. A cell-based split-luciferase system revealed that the Met–Tai complex assembled within minutes of agonist presence. To explore the potential of juvenoid peptides, we synthesized 120 new derivatives and tested them in Met–Tai interaction assays. While many substituents led to loss of activity, improved derivatives active at sub-nanomolar range outperformed hitherto existing peptidic and classical juvenoids including fenoxycarb. Their potency in inducing Met–Tai interaction corresponded with the capacity to block metamorphosis in P. apterus larvae and to stimulate oogenesis in reproductively arrested adult females. Molecular modeling demonstrated that the high potency correlates with high affinity. This is a result of malleability of the ligand-binding pocket of P. apterus Met that allows larger peptidic ligands to maximize their contact surface. Our data establish peptidic juvenoids as highly potent and species-nselective novel JHR agonists.

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

10608 - Biochemistry and molecular biology

Project

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

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2022

Confidentiality

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

Name of the periodical

Proceedings of the National Academy of Sciences of the United States of America

ISSN

0027-8424

e-ISSN

—

Volume of the periodical

119

Issue of the periodical within the volume

48

Country of publishing house

US - UNITED STATES

Number of pages

12

Pages from-to

e2215541119

UT code for WoS article

000929044100029

EID of the result in the Scopus database

2-s2.0-85142370889