Insulin receptor Arg717 and IGF-1 receptor Arg704 play a key role in ligand binding and in receptor activation

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F23%3A00577780" target="_blank" >RIV/61388963:_____/23:00577780 - isvavai.cz</a>
Alternative codes found
RIV/86652036:_____/23:00577780 RIV/00216208:11310/23:10472799
Result on the web
<a href="https://doi.org/10.1098/rsob.230142" target="_blank" >https://doi.org/10.1098/rsob.230142</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1098/rsob.230142" target="_blank" >10.1098/rsob.230142</a>

Result language
angličtina
Original language name
Insulin receptor Arg717 and IGF-1 receptor Arg704 play a key role in ligand binding and in receptor activation
Original language description
The insulin receptor (IR, with its isoforms IR-A and IR-B) and the insulin-like growth factor 1 receptor (IGF-1R) are related tyrosine kinase receptors. Recently, the portfolio of solved hormone–receptor structures has grown extensively thanks to advancements in cryo-electron microscopy. However, the dynamics of how these receptors transition between their inactive and active state are yet to be fully understood. The C-terminal part of the alpha subunit (αCT) of the receptors is indispensable for the formation of the hormone-binding site. We mutated the αCT residues Arg717 and His710 of IR-A and Arg704 and His697 of IGF-1R. We then measured the saturation binding curves of ligands on the mutated receptors and their ability to become activated. Mutations of Arg704 and His697 to Ala in IGF-1R decreased the binding of IGF-1. Moreover, the number of binding sites for IGF-1 on the His697 IGF-1R mutant was reduced to one-half, demonstrating the presence of two binding sites. Both mutations of Arg717 and His710 to Ala in IR-A inactivated the receptor. We have proved that Arg717 is important for the binding of insulin to its receptor, which suggests that Arg717 is a key residue for the transition to the active conformation.
Czech name
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Czech description
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Type
J<sub>imp</sub> - 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
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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