Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2833186 | Molecular Immunology | 2007 | 7 Pages |
Abstract
The type one complement receptor (CR1) contains a variable number of binding domains for C3b and C4b, formed through a nearly identical set of repeating units known as short consensus repeats (SCRs). Each SCR contains four cysteines that, by forming two disulfide bonds, impart a conformation critical for function. In this study, we identified a CR1 single nucleotide polymorphism (1597C > T) that results in an additional cysteine (483R > C) in SCR 8 of the N-terminal C3b/C4b binding domain, and occurring sporadically in corresponding SCRs of other repeated C3b/C4b binding domains. The normal carrier frequency for 483-C was 6.3% in 175 African Americans, and 2.4% in 153 Caucasians. In expression constructs containing one C3b/C4b binding domain, the 483-C residue reduced binding to C3b, C3bi, and C4b by over 80% (each p < 0.0001), versus the wildtype construct. Full-length CR1 from 483-C carriers also exhibited reduced binding to C3b and C4b, although the effect was influenced by the total number of binding domains present. Race-matched comparisons between SLE patients (86 African Americans, 228 Caucasians) and the normal cohort showed that 483-C carrier status alone is not a risk factor for SLE or lupus nephritis. The physiological role of this polymorphism remains to be determined.
Keywords
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Molecular Biology
Authors
Daniel J. Birmingham, Fawzi Irshaid, Katherine F. Gavit, Haikady N. Nagaraja, C. Yung Yu, Brad H. Rovin, Lee A. Hebert,