A single point mutation (Trp72-->Arg) in human apo(a) kringle 4-37 associated with a lysine binding defect in Lp(a)

• Published in: Biochimica et biophysica acta Vol. 1227; no. 1-2; pp. 41 - 45
• Main Authors: Scanu, A M, Pfaffinger, D, Lee, J C, Hinman, J
• Format: Journal Article
• Language: English
• Published: Netherlands 21.10.1994
• Subjects: Adult; Aged; Aged, 80 and over; Amino Acid Sequence; Apolipoproteins A - blood; Apolipoproteins A - chemistry; Apolipoproteins A - genetics; Base Sequence; Cardiovascular Diseases - genetics; Female; Humans; Kringles - genetics; Lipoprotein(a) - blood; Lipoprotein(a) - chemistry; Lipoprotein(a) - genetics; Male; Middle Aged; Molecular Sequence Data; Point Mutation; Sepharose - analogs & derivatives; Sepharose - chemistry; Tryptophan - chemistry
• ISSN: 0006-3002
• DOI: 10.1016/0925-4439(94)90104-X

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.