Insights into binding of S100 proteins to scavenger receptors: class B scavenger receptor CD36 binds S100A12 with high affinity

Christoph Tondera,Jens Pietzsch,Markus Laube

doi:10.1007/s00726-016-2349-2

Christoph Tondera, Jens Pietzsch + Show 1 more

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https://doi.org/10.1007/s00726-016-2349-2

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Journal: Amino acids	Publication Date: Oct 12, 2016
Citations: 61	License type: open-access

Affiliation: Helmholtz-Zentrum Dresden-Rossendorf, TU Dresden

Abstract

The EF-hand type calcium-binding protein S100A12 exerts numerous intra- and extracellular functions of (patho)physiological relevance. Therefore, receptors of S100A12 are of high interest for research and clinical applications. Beside the extensively studied receptor for advanced glycation endproducts (RAGE), G-protein coupled receptors and more recently, scavenger receptors are suggested to be putative S100A12 receptors. Own findings and further information from the literature predestined CD36, a class B scavenger receptor, as promising candidate. To substantiate or prove against this hypothesis, this study aimed at investigation of interaction of S100A12 and CD36 on molecular and cellular level by the use of surface plasmon resonance (SPR), radio- and fluorescence-tracer-based cell binding, and cell activation experiments. S100A12 revealed binding affinity to CD36 in the low nanomolar range, essentially, at the CD36 thrombospondin-1 binding site. Additionally, S100A12-mediated translocation of CD36 to the membrane and elevation of both CD36 and peroxisome proliferator-activated receptor γ (PPARγ) expression was observed, which suggest a potential regulatory function of S100A12–CD36 interaction.

Highlights

S100A12 is a member of the S100 protein family comprising more than 20 calcium-binding proteins of the EF-hand type
To check the hypothesis that CD36 is a putative S100A12 receptor, this study aimed to investigate the possible interaction of S100A12 and CD36 on molecular and cellular level by the use of surface plasmon resonance (SPR), cell association and cell activation experiments
CHOK1 showed no synthesis of receptor for advanced glycation endproducts (RAGE) in Western blot and immunocytochemistry

Summary

Introduction

S100A12 is a member of the S100 protein family comprising more than 20 calcium-binding proteins of the EF-hand type. It has to be considered that RAGE and certain scavenger receptors share a common ligand recognition principle based on electrostatic interactions between the positively charged receptor surface domains and negatively charged ligands (Adachi and Tsujimoto 2006; Jimenez-Dalmaroni et al 2009; Gao et al 2010; Fritz 2011) In this regard, there is an experimental evidence that well-characterized RAGE-ligands, such as advanced glycation endproducts, hypochlorite-modified proteins/apolipoproteins, and amyloid-β, bind to CD36 (Ohgami et al 2001; Kopprasch et al 2004; Marsche et al 2007; Jones et al 2013). There is an experimental evidence that well-characterized RAGE-ligands, such as advanced glycation endproducts, hypochlorite-modified proteins/apolipoproteins, and amyloid-β, bind to CD36 (Ohgami et al 2001; Kopprasch et al 2004; Marsche et al 2007; Jones et al 2013) Another important property RAGE and CD36 have in common is the activation of signaling cascades (Goyette et al 2009; Park 2014). S100A12 and CD36 are expressed in similar cell types, and more interestingly, the dysregulation of S100A12 and CD36 is related to similar pathological outcomes like atherosclerosis (Goyette et al 2009; Park 2014)

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