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Abstract <p>Receptor for advanced glycation endproducts (RAGE) plays an important role in the development of inflammation and neurodegenerative diseases. There is no expression of RAGE in healthy cells, but it increases during inflammation processes that leads to tissue damage. RAGE has many ligands of different classes but with similar properties, so RAGE acts as a pattern-recognition receptor. The structure of RAGE lacks information about the transmembrane domain which is necessary for signal transduction by the receptor. In this work, for the first time, using the cell-free expression method, we obtained and purified isotope-labeled fragment of RAGE (residues 335–368, corresponding to the RAGE transmembrane domain flanked by short juxtamembrane regions). For investigation of oligomerization processes we introduced a point oncogenic mutation G349R that is located in the conservative oligomerization motif GxxxG. Nuclear magnetic resonance (NMR) studies of both peptides incorporated into dodecylphosphocholine (DPC) micelles indirectly reveal changes in protein structure and oligomerization properties following the introduction of the oncogenic G349R mutation, which is thought to affect RAGE signaling.</p>

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Expression and Purification of Transmembrane Domain of RAGE for Structural-Dynamic NMR Studies

  • 期刊论文

  • 发表日期：

    2025年3月1日

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  • S. M. Dolotova,
  • D. D. Plashchinskaia,
  • Ya. V. Bershatsky,
  • V. A. Lushpa,
  • A. K. Kryuchkova,
  • D. Zhu,
  • I. S. Okhrimenko,
  • E. V. Bocharov

摘要

Abstract

Receptor for advanced glycation endproducts (RAGE) plays an important role in the development of inflammation and neurodegenerative diseases. There is no expression of RAGE in healthy cells, but it increases during inflammation processes that leads to tissue damage. RAGE has many ligands of different classes but with similar properties, so RAGE acts as a pattern-recognition receptor. The structure of RAGE lacks information about the transmembrane domain which is necessary for signal transduction by the receptor. In this work, for the first time, using the cell-free expression method, we obtained and purified isotope-labeled fragment of RAGE (residues 335–368, corresponding to the RAGE transmembrane domain flanked by short juxtamembrane regions). For investigation of oligomerization processes we introduced a point oncogenic mutation G349R that is located in the conservative oligomerization motif GxxxG. Nuclear magnetic resonance (NMR) studies of both peptides incorporated into dodecylphosphocholine (DPC) micelles indirectly reveal changes in protein structure and oligomerization properties following the introduction of the oncogenic G349R mutation, which is thought to affect RAGE signaling.