A single point mutation (Trp72-->Arg) in human apo(a) kringle 4-37 associated with a lysine binding defect in Lp(a).
Human lipoprotein(a) or Lp(a) binds, like plasminogen, to lysine Sepharose. However, contrary to plasminogen in which kringles 1 and 4 have been implicated, the binding site or sites on apo(a), the specific glycoprotein of Lp(a), have not been determined. For the first time we now report the occurrence of a human Lp(a) that has a mutant form of apo(a) where Arg has replaced Trp in position 72 of kringle 4-37 and is unable to bind to lysine Sepharose. This observation suggests that Trp72 of apo(a) kringle 4-37 may play a dominant role in lysine binding. Lysine binding has been associated with the thrombogenic potential of Lp(a). Thus, the Trp72-->Arg mutation may render Lp(a) 'benign' from the cardiovascular viewpoint.
Scanu
A M
AM
Department of Medicine, University of Chicago, IL.
Pfaffinger
D
D
Lee
J C
JC
Hinman
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001054:Apolipoproteins A / Q000097:blood / Q000737:chemistry / Q000235:genetics*; D001483:Base Sequence; D002318:Cardiovascular Diseases / Q000235:genetics; D005260:Female; D006801:Humans; D018082:Kringles / Q000235:genetics*; D017270:Lipoprotein(a) / Q000097:blood / Q000737:chemistry / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D017354:Point Mutation; D012685:Sepharose / Q000031:analogs & derivatives / Q000737:chemistry; D014364:Tryptophan / Q000737:chemistry
D001054:Apolipoproteins A; D017270:Lipoprotein(a); C030675:lysine-sepharose; D014364:Tryptophan; D012685:Sepharose