The structure, genetic polymorphisms, expression and biological functions of complement receptor type 1 (CR1/CD35)

Abstract

The complement system is comprised of soluble and cell surface associated proteins that recognize exogenous, altered, or potentially harmful endogenous ligands. In recent years, the complement system--particularly component C3 and its receptors--have been demonstrated to be a key link between innate and adaptive immunity. Complement receptor type 1 (CR1), the receptor for C3b/C4b complement peptides, has emerged as a molecule of immense interest in gaining insight to the susceptibility, pathophysiology, diagnosis, prognosis and therapy of such diseases. In this review, we wish to briefly bring forth the structure, genetic polymorphisms, expression and biological functions of CR1.

Complement receptor 1 (CR1) and Alzheimer's disease

“…1). The smaller CR1-C/F' allele has only one of these binding sites and although the functional implication of this is unclear there seems to be some sort of loss of function associated with this allele (Wong 1990;Liu and Niu 2009). Brouwers et al (2011) showed an association between one of the isoforms of CR1, CR1-B/S, and AD risk.…”

“…This functionality is also encoded in LHR-B and LHR-C. Finally, the binding sites for mannan-binding lectin (MBL) and C1q are found in the LHR-D structure (Liu and Niu 2009). …”

“…This conservation gives the repeats a structural resemblance to one another and they can be identified by the presence of two disulphide bonds at the opposite ends of a long structure. There are also several ␤-sheets and connecting loops and turns (Liu and Niu 2009). Every eighth SCR is homologous to a degree of between 65 and 100%, allowing the SCRs to be segregated into groups of seven.…”

“…The homology between every eighth SCR means that the 28 most N-terminal SCRs/CCPs are divided into four LHRs referred to as LHR-A, -B, -C and -D. This leaves a further two excluded from the LHR substructure (Fig. 2) (Klickstein et al 1988;Liu and Niu 2009). At the level of the CR1 gene, the size difference between each allele is between 1.3 and 1.5 kb, the equivalent of one LHR region in the extracellular domain of the resultant protein (Holers et al 1987).…”

Up Regulated Complement and Fc Receptors in Juvenile Idiopathic Arthritis and Correlation with Disease Phenotype

“…This might be associated with the corresponding expression of activating FcγR, as FcγR and CR1 operate in synergism to promote uptake of particles opsonized by immunoglobulin and complement proteins [26]. Nevertheless, CR1 is a multifunctional receptor, which besides phagocytosis is involved in complement regulation [27]. Thus, the increased CR1 expression may also be an attempt to down regulate the activated complement cascade, indicated by the elevated C3a levels in the JIA patients.…”