Title : N-linked glycosylation at
Asn3 and the positively charged
residues within the amino-terminal
domain of the c1 inhibitor are required for interaction of the C1 Inhibitor with Salmonella enterica serovar typhimurium lipopolysaccharide and lipid A
Abstract :
- The C1 inhibitor ( C1INH ), a plasma complement regulatory protein , prevents endotoxin shock, at least partially via the direct interaction of its amino-terminal heavily glycosylated nonserpin region with gram-negative bacterial lipopolysaccharide (LPS)
- To further characterize the potential LPS-binding site(s) within the amino-terminal domain , mutations were introduced into C1INH at the three N-linked glycosylation sites and at the four positively charged amino acid residues
- A mutant in which Asn(3) was replaced with Ala was markedly less effective in its binding to LPS, while substitution of Asn(47) or Asn(59) had little effect on binding
- The mutation of C1INH at all four positively charged amino acid residues ( Arg(18), Lys(22), Lys(30), and Lys(55) ) resulted in near-complete failure to interact with LPS
- The C1INH mutants that did not bind to LPS also did not suppress LPS binding or LPS-induced up-regulation of tumor necrosis factor alpha mRNA expression in RAW 264.7 macrophages
- In addition, the binding of C1INH mutants to diphosphoryl lipid A was decreased in comparison with that of recombinant wild-type C1INH
- Therefore, the interaction of C1INH with gram-negative bacterial LPS is dependent both on the N-linked carbohydrate at Asn(3) and on the positively charged residues within the amino-terminal domain
Output (sent_index, trigger,
protein,
sugar,
site):
- 0. glycosylation, , -, -, Asn3
- 1. glycosylated, , -, -, region
- 2. glycosylation, , -, -, sites
- 7. Asn, , -, the N-linked carbohydrate, Asn(3)
Output(Part-Of) (sent_index,
protein,
site):
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):
- 0. C1INH, -, Asn3
- 7. C1INH, the N-linked carbohydrate, Asn(3)