Identification of Amino Acid Residues Involved in the pH Sensitivity of Receptor Tyrosine Kinase IRR

IF 1.1 Q4 CELL BIOLOGY

Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Pub Date : 2025-04-24 DOI:10.1134/S1990747824700430

A. A. Gavrilenkova, D. A. Krivosheina, V. A. Pyatkina, E. V. Bocharov, I. E. Deyev

引用次数: 0

Abstract

IRR is a member of the insulin receptor (IR) family that has no known endogenous peptide agonists but can be activated by weak alkaline environments and has thus been proposed to function as an extracellular pH sensor. IRR activation by alkali is determined by its N-terminal extracellular region. Using recently published Cryo-EM structure of IRR ectodomain we identify three amino acids (R87, K143 and S516) that may be involved in the IRR activation by alkali. In this report we show that the triple substitution of these amino acids with alanine leads to complete disappearance of the IRR pH sensitivity. Thus, these amino acids can form one of the possible pH sensor sites in the IRR molecule.

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受体酪氨酸激酶 IRR 的 pH 敏感性所涉及的氨基酸残基的鉴定

IRR是胰岛素受体（IR）家族的一员，没有已知的内源性肽激动剂，但可以被弱碱性环境激活，因此被认为是细胞外pH传感器。碱对IRR的激活是由它的n端胞外区决定的。利用最近发表的IRR外结构域的cro - em结构，我们鉴定了可能参与碱激活IRR的三个氨基酸（R87， K143和S516）。在这篇报告中，我们发现这些氨基酸与丙氨酸的三重取代导致IRR pH敏感性完全消失。因此，这些氨基酸可以在IRR分子中形成可能的pH传感器位点之一。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology CELL BIOLOGY-

CiteScore

1.40

自引率

0.00%

发文量

期刊介绍： Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology is an international peer reviewed journal that publishes original articles on physical, chemical, and molecular mechanisms that underlie basic properties of biological membranes and mediate membrane-related cellular functions. The primary topics of the journal are membrane structure, mechanisms of membrane transport, bioenergetics and photobiology, intracellular signaling as well as membrane aspects of cell biology, immunology, and medicine. The journal is multidisciplinary and gives preference to those articles that employ a variety of experimental approaches, basically in biophysics but also in biochemistry, cytology, and molecular biology. The journal publishes articles that strive for unveiling membrane and cellular functions through innovative theoretical models and computer simulations.