Mutations at hypothetical binding site 2 in insulin and insulin-like growth factors 1 and 2

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F23%3A00575692" target="_blank" >RIV/61388963:_____/23:00575692 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1016/bs.vh.2023.01.010" target="_blank" >https://doi.org/10.1016/bs.vh.2023.01.010</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/bs.vh.2023.01.010" target="_blank" >10.1016/bs.vh.2023.01.010</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Mutations at hypothetical binding site 2 in insulin and insulin-like growth factors 1 and 2

Popis výsledku v původním jazyce

Elucidating how insulin and the related insulin-like growth factors 1 and 2 (IGF-1 and IGF-2) bind to their cellular receptors (IR and IGF-1R) and how the receptors are activated has been the holy grail for generations of scientists. However, deciphering the 3D structure of tyrosine kinase receptors and their hormone-bound complexes has been complicated by the flexible and dimeric nature of the receptors and the dynamic nature of their interaction with hormones. Therefore, mutagenesis of hormones and kinetic studies first became an important tool for studying receptor interactions. It was suggested that hormones could bind to receptors through two binding sites on the hormone surface called site 1 and site 2. A breakthrough in knowledge came with the solution of cryoelectron microscopy (cryoEM) structures of hormone-receptor complexes. In this chapter, we document in detail the mutagenesis of insulin, IGF-1, and IGF-2 with emphasis on modifications of the hypothetical binding site 2 in the hormones, and we discuss the results of structure-activity studies in light of recent cryoEM structures of hormone complexes with IR and IGF-1R.

Název v anglickém jazyce

Mutations at hypothetical binding site 2 in insulin and insulin-like growth factors 1 and 2

Popis výsledku anglicky

Elucidating how insulin and the related insulin-like growth factors 1 and 2 (IGF-1 and IGF-2) bind to their cellular receptors (IR and IGF-1R) and how the receptors are activated has been the holy grail for generations of scientists. However, deciphering the 3D structure of tyrosine kinase receptors and their hormone-bound complexes has been complicated by the flexible and dimeric nature of the receptors and the dynamic nature of their interaction with hormones. Therefore, mutagenesis of hormones and kinetic studies first became an important tool for studying receptor interactions. It was suggested that hormones could bind to receptors through two binding sites on the hormone surface called site 1 and site 2. A breakthrough in knowledge came with the solution of cryoelectron microscopy (cryoEM) structures of hormone-receptor complexes. In this chapter, we document in detail the mutagenesis of insulin, IGF-1, and IGF-2 with emphasis on modifications of the hypothetical binding site 2 in the hormones, and we discuss the results of structure-activity studies in light of recent cryoEM structures of hormone complexes with IR and IGF-1R.

Druh

C - Kapitola v odborné knize

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

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

Název knihy nebo sborníku

Hormone Receptors: Structures and Functions

ISBN

978-0-443-13455-5

Počet stran výsledku

44

Strana od-do

187-230

Počet stran knihy

662

Název nakladatele

Elsevier

Místo vydání

Cambridge

Kód UT WoS kapitoly

001101822300007