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

Kertisová, Anna; Žáková, Lenka; Macháčková, Kateřina; Marek, Aleš; Šácha, Pavel; Pompach, Petr; Jiráček, Jiří; Selicharová, Irena

doi:https://dx.doi.org/10.1098/rsob.230142

Number of the records: 1

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

1.

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, ORCID}
Article 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

Number of the records: 1