Modeling the interaction between quinolinate and the receptor for advanced glycation end products (RAGE): relevance for early neuropathological processes

PloS One
Iris N SerratosAbel Santamaria

Abstract

The receptor for advanced glycation end products (RAGE) is a pattern-recognition receptor involved in neurodegenerative and inflammatory disorders. RAGE induces cellular signaling upon binding to a variety of ligands. Evidence suggests that RAGE up-regulation is involved in quinolinate (QUIN)-induced toxicity. We investigated the QUIN-induced toxic events associated with early noxious responses, which might be linked to signaling cascades leading to cell death. The extent of early cellular damage caused by this receptor in the rat striatum was characterized by image processing methods. To document the direct interaction between QUIN and RAGE, we determined the binding constant (Kb) of RAGE (VC1 domain) with QUIN through a fluorescence assay. We modeled possible binding sites of QUIN to the VC1 domain for both rat and human RAGE. QUIN was found to bind at multiple sites to the VC1 dimer, each leading to particular mechanistic scenarios for the signaling evoked by QUIN binding, some of which directly alter RAGE oligomerization. This work contributes to the understanding of the phenomenon of RAGE-QUIN recognition, leading to the modulation of RAGE function.

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Citations

Jul 1, 2015·Neurochemistry International·Ana Laura Colín-GonzálezAbel Santamaría
May 23, 2016·Arthritis Research & Therapy·Yessica Zamudio-CuevasAlberto López-Reyes
Oct 26, 2016·Oxidative Medicine and Cellular Longevity·Denise Clavijo-CornejoAlberto López-Reyes
May 10, 2017·Journal of Medicinal Chemistry·Salvatore BongarzoneAntony D Gee
Aug 10, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Meghan T LogunLohitash Karumbaiah
Jul 3, 2021·International Journal of Molecular Sciences·Hyeon Jin KimSe Bok Jang

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Methods Mentioned

BETA
X-ray
NMR
glycosylation

Software Mentioned

LIGPLOT
ACD
AutoDock Vina
Carestream Molecular Imaging
ImageJ
QUIN
RAGE
NAMD
LIGPLOT +
MatchMaker

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