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

Biochim Biophys Acta. 1994 Oct 21;1227(1-2):41-5. doi: 10.1016/0925-4439(94)90104-x.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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

Substances

  • Apolipoproteins A
  • Lipoprotein(a)
  • lysine-sepharose
  • Tryptophan
  • Sepharose