Accepted_test

Study of the mechanisms of activation of the insulin receptor (IR) using mutant forms of the receptor

Authors:
Gavrilenkova Alina, Moscow Institute of Physics and Technology; Shemyakin–Ovchinnikov Institute of bioorganic chemistry RAS
Deyv Igor, Shemyakin–Ovchinnikov Institute of bioorganic chemistry RAS
Bocharov Eduard, Moscow Institute of Physics and Technology; Shemyakin–Ovchinnikov Institute of bioorganic chemistry RAS
Serova Oksana, Shemyakin–Ovchinnikov Institute of bioorganic chemistry RAS

Abstract ID: 169

Event: BGRS-abstracts

Sections: [Sym 3] Section “Structural biology of proteins nucleic acids and membranes”

The insulin receptor (IR) plays a key role in regulating metabolism. At the moment, the exact mechanisms of conformational changes in IR during its activation are still being investigated.
In this work, the activation of the IR receptor with amino acid residue substitutions in the transmembrane domain was analyzed. It was found that the double substitution of I951E-F952R and single substitutions of I951E and F952R lead to autophosphorylation of the receptor in the absence of a ligand. It has been shown that phosphorylation of the IR receptor with a double I951E-F952R and single I951E and F952R substitutions in the absence of a ligand leads to activation of intracellular signaling proteins IRS-1 and Erk, which confirms the functional activity of mutant forms of IR. For further structural analysis, eukaryotic cell lines constitutively expressing the IR receptor and its mutant form I951E-F952R were obtained. The data obtained indicate the important role of the transmembrane domain in the activation of the insulin receptor.