Eosinophil cationic protein (ECP) can bind heparin and other glycosaminoglycans through its RNase active site.
The eosinophil cationic protein (ECP) is an eosinophil-secreted RNase involved in the immune host defense, with a cytotoxic activity against a wide range of pathogens. During inflammation and eosinophilia disorders, ECP is secreted to the inflammation area, where it would contribute to the immune response. ECP secretion causes also severe damage to the host own tissues. ECP presents a high affinity for heparin and this property might be crucial for its immunomodulating properties, antipathogen action, and its toxicity against eukaryotic cells. ECP, also known as human RNase 3, belongs to the mammalian RNase A superfamily and its RNase activity is required for some of its biological properties. We have now proven that ECP heparin binding affinity depends on its RNase catalytic site, as the enzymatic activity is blocked by heparin. We have applied molecular modeling to analyze ECP binding to heparin representative probes, and identified protein residues at the catalytic and substrate binding sites that could contribute to the interaction. ECP affinity for heparin and other negatively charged glycosaminoglycans (GAGs) can explain not only its binding to the eukaryote cells glycocalix but also the reported high affinity for the specific carbohydrates at bacteria cell wall, promoting its antimicrobial action.
Torrent
Marc
M
Dpt. Bioquímica i Biologia Molecular, Fac. Biociències, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallés, Spain.
Nogués
M Victòria
MV
Boix
Ester
E
D020134:Catalytic Domain; D047150:Eosinophil Cationic Protein / Q000737:chemistry / Q000378:metabolism*; D005454:Fluorescence Polarization; D006025:Glycosaminoglycans / Q000737:chemistry / Q000378:metabolism*; D006493:Heparin / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D012260:Ribonucleases / Q000737:chemistry / Q000378:metabolism*
D006025:Glycosaminoglycans; D006493:Heparin; D012260:Ribonucleases; D047150:Eosinophil Cationic Protein