In studies conducted about 8 years ago, the author and her colleagues raised a
monoclonal antibody that recognized an uncharacterized human platelet
protein with a reduced molecular mass of 155 kDa. Investigations of this
protein's nonreduced structure yielded surprising findings: in its native state, it exists as massive
disulfide-linked multimers millions of daltons in size, making it one of the largest
proteins found in the human body. This feature led the author to designate this
protein "
multimerin."
Multimerin is found in endothelial cells as well as in platelets. It originates from a single
subunit protein, promultimerin, that undergoes extensive N-glycosylation, proteolytic processing and polymerization during biosynthesis. Recent data from the cloning and sequencing of its
complementary DNA indicate that
multimerin is a unique
protein. Like
von Willebrand factor, it has a massive repeating structure, but these
proteins are unrelated.
Multimerin's sequence contains the adhesive motif
Arg-Gly-Asp-Ser, central coiled-coil sequences, several
epidermal growth-factor-like motifs, and a globular domain that is similar to a protein-binding domain found in
complement C1q and in
collagens type VIII and X. Investigations of
multimerin's function indicate that it binds the coagulation
protein factor V and its activated form,
factor Va. In platelets, but not in plasma, all of the biologically active
factor V is complexed with
multimerin.
Multimerin may also have functions as an extracellular matrix or adhesive
protein. Recently, members of 2 Canadian families with puzzling autosomal-dominant
bleeding disorders were found to have a deficiency of platelet
multimerin. Studies of these patients may provide a unique opportunity to evaluate the functions of
multimerin.