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) are human plasma proteins with regulatory functions in the alternative pathway of complement activation. FH and FHL-1 are organized in repetitive elements 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 fourth SCR of both proteins (SCR 4) includes the sequence Arg-Gly-Asp (RGD), a motif that is responsible for the major adhesive activity of matrix proteins like fibronectin. A synthetic hexapeptide with the sequence ERGDAV derived from the RGD domain of FH/FHL-1 interferes with cell attachment to a fibronectin matrix. Although the identical motif is present in both FH and FHL-1, only FHL-1 acts as a matrix for cell spreading and attachment, thus the two proteins differ in function. The adhesive activity of FHL-1 is localized to the RGD-containing SCR 4 by the use of recombinant fragments. All three analysed anchorage-dependent cell lines (CCl64, C32 and MRC-5) adhere to an FHL-1 matrix. The use 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 integrin 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.
Hellwage
J
J
Bernhard Nocht Institute for Tropical Medicine, Hamburg, Federal Republic of Germany.
Kühn
S
S
Zipfel
P F
PF
D000818:Animals; D001798:Blood Proteins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D017242:Complement Factor H / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004848:Epithelium; D005347:Fibroblasts; D006801:Humans; D008545:Melanoma; D008907:Mink; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D014407:Tumor Cells, Cultured
D001798:Blood Proteins; C493495:CFH protein, human; D010446:Peptide Fragments; C100631:factor H-related protein 1; D004533:Egtazic Acid; D017242:Complement Factor H; D004492:Edetic Acid