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Insulin receptor Arg717 and IGF-1 receptor Arg704 play a key role in ligand binding and in receptor activation
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SYSNO ASEP 0577780 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Insulin receptor Arg717 and IGF-1 receptor Arg704 play a key role in ligand binding and in receptor activation Author(s) Kertisová, Anna (UOCHB-X)
Žáková, Lenka (UOCHB-X) RID, ORCID
Macháčková, Kateřina (UOCHB-X)
Marek, Aleš (UOCHB-X) RID, ORCID
Šácha, Pavel (UOCHB-X) RID, ORCID
Pompach, Petr (BTO-N)
Jiráček, Jiří (UOCHB-X) RID, ORCID
Selicharová, Irena (UOCHB-X) RID, ORCIDArticle number 230142 Source Title Open Biology. - : Royal Society Publishing
Roč. 13, č. 11 (2023)Number of pages 14 s. Language eng - English Country GB - United Kingdom Keywords mutagenesisin vitro ; peptide hormone ; eceptor modification ; eceptor tyrosine kinase ; structure–function OECD category Biochemistry and molecular biology R&D Projects LX22NPO5104 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) EF16_019/0000729 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) GA22-17978S GA ČR - Czech Science Foundation (CSF) EF18_046/0015974 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LM2023042 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support UOCHB-X - RVO:61388963 ; BTO-N - RVO:86652036 UT WOS 001100817800006 EID SCOPUS 85176313303 DOI 10.1098/rsob.230142 Annotation 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. Workplace Institute of Organic Chemistry and Biochemistry Contact asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Year of Publishing 2024 Electronic address https://doi.org/10.1098/rsob.230142
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