Binding site on human C-reactive Protein (CRP) recognized by the Leukocyte CRP-receptor
✍ Scribed by Qin Zen; Wangjian Zhong; Richard F. Mortensen
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 135 KB
- Volume
- 64
- Category
- Article
- ISSN
- 0730-2312
No coin nor oath required. For personal study only.
✦ Synopsis
C-reactive protein (CRP), the prototypical inflammatory acute phase reactant in humans, interacts with monocytes and neutrophils via a specific receptor. To map the site on CRP recognized by the CRP receptor (CRP-R), synthetic peptides corresponding to the surface region on each of the five identical subunits were tested as competitors vs. [ 125 I]-CRP for cell binding. A peptide of residues 27-38 (TKPLKAFTVCLH) efficiently inhibited CRP binding when compared to other nonoverlapping peptides. This peptide was termed the cell-binding peptide (CB-Pep). The F(ab8) 2 of an IgG Ab to the CB-Pep specifically inhibited CRP binding upon reacting with the ligand. Competitive binding studies with synthetic peptides truncated from either the NH 2 -or COOH-terminus of the CB-Pep revealed that the minimum length recognized by the CRP-R consisted of residues 31-36: KAFTVC. Conservative substitutions of residues within the CB-Pep indicated that the four residues AFTV were critical for CRP-R binding. The CB-Pep also inhibited induced superoxide generation by HL-60 granulocytes. The minimum length required for the inhibition was also KAFTVC; however, only Phe-33 and Leu-37 were critical residues in this assay. Anti-CB-Pep IgG Ab reacted more extensively with heat-modified CRP, suggesting that an altered conformation of CRP is preferentially recognized by the CRP-R. The results suggest that this contiguous sequence on a b-strand on one face of each of five subunits of the CRP pentamer serves as a unique recognition motif for inflammatory leukocytes.