THE HUMAN-COMPLEMENT REGULATORY FACTOR-H-LIKE PROTEIN-1, WHICH REPRESENTS A TRUNCATED FORM OF FACTOR-H, DISPLAYS CELL-ATTACHMENT ACTIVITY

Complement factor H (FH) and factor-H-like protein 1 (FHL-1) an human plasma proteins with regulatory functions in the alternative pathway o f complement activation. FH and FHL-1 are organized in repetitive elem ents termed short consensus repeats (SCRs) and the seven SCRs of FHL-1 are identical with the N-terminal domain of the 20 SCRs of FH. The fo urth SCR of both proteins (SCR 4) includes the sequence Arg-Gly-Asp (R GD), a motif that is responsible for the major adhesive activity of ma trix proteins like fibronectin. A synthetic hexapeptide with the seque nce ERGDAV derived from the RGD domain of FH/FHL-1 interferes with cel l attachment to a fibronectin matrix. Although the identical motif is present in both FK and FHL-1, only FHL-1 acts as a matrix for cell spr eading and attachment, thus the two proteins differ in function. The a dhesive activity of FHL-1 is localized to the RGD-containing SCR 4 by the use of recombinant fragments. All three analysed anchorage-depende nt cell lines (CC164, C32 and MRC-5) adhere to an FHL-1 matrix. The us e of synthetic peptides in competition assays, on either FHL-1-derived or fibronectin matrices, shows that the cellular receptors binding to the FH/FHL-1-derived RGD motif are related to or identical with integ rin receptors which interact with fibronectin. The identification of a functional adhesive domain in the FH/FHL-1 sequence demonstrates, at least for FHL-1, a role in cell attachment and adhesion.