Minimum stable structure of the receptor for advanced glycation end product possesses multi ligand binding ability

Biochem Biophys Res Commun. 2009 Aug 14;386(1):130-4. doi: 10.1016/j.bbrc.2009.05.142. Epub 2009 Jun 6.

Abstract

The receptor for advanced glycation end products (RAGE) is a multi-ligand receptor involved in the development of diabetic complications. Although the soluble form of the extracellular domain maintains the ability to bind multi-ligands, it is unstable and degrades into several peptide species during storage. Proteolysis with thrombin or factor Xa revealed several protease sensitive sites. Most sensitive site is located between Arg228 and Val229, and peptide bond next to Arg216, Arg116, Arg114 and Trp271 are also cleaved. Seven truncated extracellular domains of RAGE were engineered in order to obtain a stable soluble fragment. RAGE 143 (Ala23-Thr143) is not only protease resistant but also shows the same ligand-binding ability as that of the full-length extracellular domain. The resultant minimum RAGE 143 works as a stable recognition devise to detect advanced glycation end products (AGEs).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Factor Xa / chemistry
  • Glycation End Products, Advanced / chemistry
  • Glycation End Products, Advanced / metabolism
  • Humans
  • Ligands
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / chemistry*
  • Receptors, Immunologic / genetics
  • Thrombin / chemistry

Substances

  • Glycation End Products, Advanced
  • Ligands
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic
  • Thrombin
  • Factor Xa