Preferential binding and aggregation of rabbit C-reactive protein with arginine-rich proteins

Abstract

Human and rabbit C-reactive proteins (CRP) are similar in mol. wt, structure and amino acid sequence. In addition to the characteristic phosphoryline (PC)-binding specificity, both CRP molecules bind arginine- and lysine-rich proteins. The human CRP-cationic protein reactivity has been reported to be inhibited by calcium and promoted by PC in the presence of calcium. The present study compares binding and precipitation reactions of rabbit CRP (raCRP) with arginine- and lysine-rich proteins, and demonstrates the differential modulation of these interactions by calcium and acidic pH. Rabbit CRP shows preferential binding and precipitation reactivities with arginine-rich cationic molecules. Binding of raCRP to poly- l-arginine (PLA) and arginine-rich histone (ARH) occurs at pH 6.0, in the presence of calcium and is inhibitable by phosphorylcholine (PC) suggesting an interaction at or near the calcium-modulated PC binding site. The in vitro precipitation of raCRP and arginine-rich cationic molecules is significantly inhibited at pH 6.0, by the non-precipitating lysine-rich ligand PLL, and by physiological levels of calcium, and may reflect the participation of distinct “self-aggregation” sites on CRP in the precipitation response. The significance of the preferential arginine reactivity of raCRP to in vivo functions as a scavenger of chromatin during cell death and/or as a modulator of lipoprotein metabolism during the acute phase response is discussed.