A Short Consensus Repeat-Containing Complement Regulatory Protein of Lamprey That Participates in Cleavage of Lamprey Complement 3

Abstract

The prototype of the short consensus repeat (SCR)-containing C regulatory protein is of interest in view of its evolutionary significance with regard to the origin of the C regulatory system. Lamprey is an agnathan fish that belongs to the lowest class of vertebrates. Because it does not possess lymphocytes, it lacks Ig and consequently the classical C pathway. We identified an SCR-containing C regulatory protein from the lamprey. The primary structure predicted from the cDNA sequence showed that this is a secretary protein consisting of eight SCRs. This framework is similar to the α-chain of C4b-binding protein (C4bp). SCR2 and -3 of human C4bp are essential for C4b inactivation, and this region is fairly well conserved in the lamprey protein. However, the other SCRs of this protein are similar to those of other human C regulatory proteins. The lamprey protein binds to the previously reported lamprey C3b/C3bi deposited on yeast and cleaves lamprey C3b-like C3 together with a putative serum protease. The scheme resembles the C regulatory system of mammals, where factor I and its cofactor inactivate C3b. Unlike human cofactors, the lamprey protein requires divalent cations for C3b-like C3 cleavage. Its artificial membrane-anchored form protects host cells from lamprey C attack via the lectin pathway. Thus, the target of this protein appears to be C3b and/or its family. We named this protein Lacrep, the lamprey C regulatory protein. Lacrep is a member of SCR-containing C regulators, the first of its kind identified in the lowest vertebrates.

Sensing Bacterial Flagellin by Membrane and Soluble Orthologs of Toll-like Receptor 5 in Rainbow Trout (Onchorhynchus mikiss)

“…7A). The amounts of bound proteins were compared with that of lamprey complement 3 (AY359861) (20), which do not bind GST-FlaA. The binding assay suggested that rtTLR5S has sufficient affinity to hold flagellin.…”

A CD46-like Molecule Functional in Teleost Fish Represents an Ancestral Form of Membrane-Bound Regulators of Complement Activation

“…As for function of RCA in the lower vertebrates, regulatory roles in deposition of C3 and degradation of C3b/C4b have been described only for secreted RCAs in lamprey (35) and barred sand bass (28)(29)(30). No functional data, in contrast, have been reported for membrane-bound RCA protein in any lower vertebrate species.…”

“…Calcein release cytotoxicity test was performed, as described elsewhere (35). Briefly, transfected CHO cells (1.0 3 10 4 cells) were seeded in each well of 96-well plates and cultured overnight at 37˚C in 5% CO 2 .…”

“…Phylogenetic and genomic lines of evidence have indicated that RCA had emerged in cyclostome, the most ancient class of vertebrate (35), and that bony fish are equipped with both group 1 and group 2 RCAs, because factor H-like secreted RCAs and membrane-bound RCAs have been found in zebrafish genome (33,34). As for function of RCA in the lower vertebrates, regulatory roles in deposition of C3 and degradation of C3b/C4b have been described only for secreted RCAs in lamprey (35) and barred sand bass (28)(29)(30).…”

Novel Complement Factor H mutation, a case report of atypical hemolytic uremic syndrome

“…It is characterized by expressing specific domains: short consensus repeat (SCR) or control unit complement proteins (CCP). [11,14,15] Factor H contains 20 of these domains (see Figure 2). Figure 2.…”