Molecular Basis for the Involvement of Mammalian Serum Albumin in the AGE/RAGE Axis: A Comprehensive Computational Study

Date

2024-03-11

Advisors

Journal Title

Journal ISSN

ISSN

1422-0067

Volume Title

Publisher

MPDI

Type

Article

Peer reviewed

Yes

Abstract

In mammals, glycated serum albumin (gSA) contributes to the pathogenesis of many metabolic diseases by activating the receptors (RAGE) for advanced glycation end products (AGEs). Many aspects of the gSA–RAGE interaction remain unknown. The purpose of the present paper was to study the interaction of glycated human albumin (gHSA) with RAGE using molecular modeling methods. Ten models of gHSA modified with different lysine residues to carboxymethyl-lysines were prepared. Complexes of gHSA–RAGE were obtained by the macromolecular docking method with subsequent molecular dynamics simulation (MD). According to the MD, the RAGE complexes with gHSA glycated at Lys233, Lys64, Lys525, Lys262 and Lys378 are the strongest. Three-dimensional models of the RAGE dimers with gHSA were proposed. Additional computational experiments showed that the binding of fatty acids (FAs) to HSA does not affect the ability of Lys525 (the most reactive lysine) to be glycated. In contrast, modification of Lys525 reduces the affinity of albumin for FA. The interspecies differences in the molecular structure of albumin that may affect the mechanism of the gSA–RAGE interaction were discussed. The obtained results will help us to learn more about the molecular basis for the involvement of serum albumin in the AGE/RAGE axis and improve the methodology for studying cellular signaling pathways involving RAGE.

Description

open access article

Keywords

carboxymethyl-lysine;, diabetes mellitus, fatty acids;, glycated albumin, macromolecular docking, molecular dynamics, receptor for advanced glycation end products

Citation

Belinskaia, D.A.; Jenkins, R.O.; Goncharov, N.V. (2024) Molecular basis for the involvement of mammalian serum albumin in the AGE/RAGE axis: a comprehensive computational study. International Journal of Molecular Sciences, 25 (6), 3204

Rights

Research Institute