Characterization of αX I-Domain Binding to Receptors for Advanced Glycation End Products (RAGE)
Autor: | Sang-Uk Nham, Dolgorsuren Buyannemekh |
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Rok vydání: | 2017 |
Předmět: |
binding
I-domain leukocytes Recombinant Fusion Proteins Antigen presentation Integrin Receptor for Advanced Glycation End Products Integrin alphaXbeta2 02 engineering and technology 01 natural sciences Article Protein Domains Glycation Humans Receptor Molecular Biology Alanine chemistry.chemical_classification Binding Sites biology Chemistry Cell adhesion molecule 010401 analytical chemistry Cell Biology General Medicine Surface Plasmon Resonance 021001 nanoscience & nanotechnology Transmembrane protein β2 integrin RAGE 0104 chemical sciences Cell biology Amino acid Kinetics Amino Acid Substitution Mutation biology.protein 0210 nano-technology |
Zdroj: | Molecules and Cells |
ISSN: | 0219-1032 |
Popis: | The β2 integrins are cell surface transmembrane proteins regulating leukocyte functions, such as adhesion and migration. Two members of β2 integrin, αMβ2 and αXβ2, share the leukocyte distribution profile and integrin αXβ2 is involved in antigen presentation in dendritic cells and transendothelial migration of monocytes and macrophages to atherosclerotic lesions. Receptor for advanced glycation end products (RAGE), a member of cell adhesion molecules, plays an important role in chronic inflammation and atherosclerosis. Although RAGE and αXβ2 play an important role in inflammatory response and the pathogenesis of atherosclerosis, the nature of their interaction and structure involved in the binding remain poorly defined. In this study, using I-domain as a ligand binding motif of αXβ2, we characterize the binding nature and the interacting moieties of αX I-domain and RAGE. Their binding requires divalent cations (Mg2+ and Mn2+) and shows an affinity on the sub-micro molar level: the dissociation constant of αX I-domains binding to RAGE being 0.49 μM. Furthermore, the αX I-domains recognize the V-domain, but not the C1 and C2-domains of RAGE. The acidic amino acid substitutions on the ligand binding site of αX I-domain significantly reduce the I-domain binding activity to soluble RAGE and the alanine substitutions of basic amino acids on the flat surface of the V-domain prevent the V-domain binding to αX I-domain. In conclusion, the main mechanism of αX I-domain binding to RAGE is a charge interaction, in which the acidic moieties of αX I-domains, including E244, and D249, recognize the basic residues on the RAGE V-domain encompassing K39, K43, K44, R104, and K107. |
Databáze: | OpenAIRE |
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