Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Frank, S; Durovic, S; Kostner, GM.
Structural requirements of apo-a for the lipoprotein-a assembly.
Biochem J. 1994; 304 ( Pt 1)(3):27-30
Doi: 10.1042/bj3040027
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- Führende Autor*innen der Med Uni Graz
- Frank Sasa
- Kostner Gerhard
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- Abstract:
- Lipoprotein-a [Lp(a)], one of the most atherogenic lipoproteins, is composed of a low-density lipoprotein (LDL) core in addition to an apo-a of variable size which is linked to apoB by a disulphide bridge. Lp(a) synthesized in vitro by incubation of recombinant apo-a (r-apo-a) with LDL is physico-chemically indistinguishable from native Lp(a). The synthesis of Lp(a) in vitro proceeds in two steps. In the first step, one of the unique kringle-IVs (K-IVs) in apo-a binds to a Lys residue of apoB; in the second step, Cys-4057 of K-IV type-9 (T-9) forms a disulphide bridge with Cys-3734 of LDL. Here we have produced r-apo-a with different combinations of unique K-IVs and shown that K-IV T-6 is required for the first step of Lp(a) assembly. For the second step not only is K-IV T-9 essential, but also the distance between T-6 and T-9 requires a length of two K-IVs. These findings give additional insight into the mode of Lp(a) assembly and are of relevance in the search for apo-a mutants influencing Lp(a) levels and for the development of Lp(a)-lowering medications.
- Find related publications in this database (using NLM MeSH Indexing)
- Blotting, Western -
- Cell Line -
- DNA, Complementary -
- Humans -
- Lipoprotein(a) - chemistry
- Lipoproteins, LDL - chemistry