Original title: Role Argininu 717 v inzulínovém receptoru, respektive Argininu 704 v IGF-1 receptoru při vazbě ligandů
Translated title: Role of Arginine 717 in insulin receptor respective Arginine 704 in IGF-1 receptor for the interaction with ligands
Authors: Kertisová, Anna ; Selicharová, Irena (advisor) ; Ryšlavá, Helena (referee)
Document type: Master’s theses
Year: 2023
Language: cze
Abstract: [cze] [eng]
Inzulín a homologický inzulínu podobný rustový faktor 1 (IGF-1) jsou peptidove hormoný, ktere jsou významnými regulatorý bunecneho metabolismu, proliferace a apoptozý. Poruchý v signalizacních drahach techto hormonu s sebou nesou radu zavazných onemocnení od diabetu mellitu týpu 1 a 2 po rakovinne bujení ci neurodegenerativní onemocnení. Bunecnou odpoveď na týto hormoný zprostredkovavají inzulinove (IR) a IGF-1 receptorý (IGF-1R) s týrozinkinazovou aktivitou. Receptorý tvorí heterotetramerý dvou extracelularních α podjednotek a intracelularních β podjednotek. Studium struktur receptoru se snazí ozrejmit zakladní princip interakce receptoru s jejich ligandý, avsak stale zustava role nekterých aminokýselinových zbýtku ve vazbe hormonu neobjasnena. Predpoklada se, ze arginin 704 IGF-1R bý se mohl ucastnit interakce s glutaminem 58 IGF-1. Na rozdíl od IGF-1R nebýl ekvivalentní arginin 717 IR v predchozích studiích pokladan za dulezitý pro vazbu inzulínu. Tato prace se zabýva objasnením role argininu 704 IGF-1R, a pro porovnaní analogický argininu 717 IR izoformý A (IR-A), ve vazbe ligandu na receptor. Býlý výtvorený mutantní variantý IGF-1R na pozicích His697 a Arg704 a variantý IR-A na pozicích His710 a Arg717. Role histidinu 697 IGF-1R a 710 IR jiz býla dríve objasnena, proto jejich aminokýselinova... Insulin and insulin-like growth factor 1 (IGF-1) are peptide hormones that are important regulators of cellular metabolism, proliferation and apoptosis. Disruptions in signalling pathways may cause a whole range of diseases from diabetes mellitus type 1 and type 2 to cancer or neurodegenerative diseases. The cellular response to these hormones is mediated by insulin (IR) and IGF-1 receptors (IGF-1R) with a tyrosin-kinase activity. Receptors are created as hetero-tetramers of two extracellular α-subunits and two intracellular β-subunits. Studies of receptor structures try to elucidate the basic principles of the interaction of receptors with their ligands. However, the role of some amino-acid residues in binding remains unclear. It was suggested that the arginine 704 of IGF-1R may interact with Glu58 IGF-1. In comparison with IGF-1R, the equivalent arginine 717 IR was not associated with an important role in insulin binding in previous studies. This thesis is focused on clarifying the role of Arg704 IGF-1R and for comparison analogically on Arg717 IR isoform A (IR-A) in ligand binding to the receptors. Therefore, mutant variants of IGF-1R in positions His697 and Arg704 and variants IR-A in positions His710 and Arg717 were created. The role of histidines 697 IGF-1R and 710 IR was already elucidated...
Keywords: complex ligand-receptor; IGF-1; IGF-1 receptor; insulin; insulin receptor; saturation binding assay; site-directed mutagenesis; IGF-1; IGF-1 receptor; inzulín; inzulínový receptor; komplex ligand-receptor; místně specifická mutageneze; saturační vazebná zkouška

Institution: Charles University Faculties (theses) (web)
Document availability information: Available in the Charles University Digital Repository.
Original record: http://hdl.handle.net/20.500.11956/181247

Permalink: http://www.nusl.cz/ntk/nusl-528056


The record appears in these collections:
Universities and colleges > Public universities > Charles University > Charles University Faculties (theses)
Academic theses (ETDs) > Master’s theses