CRYSTAL STRUCTURE OF THE RECEPTOR-BINDING DOMAIN OF BOVINE a2-MACROGLOBULIN

Lasse Jenner, Lise Husted, Soren Thirp, Lars Sottrup-Jensen and Jens Nyborg.

IMSB, Science Park Division, University of Aarhus, DK-8000 Aarhus C. e-mail: lbj@imsb.au.dk

Keywords: Macroglobulins, Proteinase Inhibitor.

The large plasma proteinase inhibitors of the a2-macroglobulin super family inhibit proteinases by capturing them inside a central cavity of the molecule. After reaction with the proteinase the circulating a-macroglobulin-proteinase complex is rapidly cleared by binding to the a-macroglobulin receptor present in the liver and other tissues through recognition sites located on a separate approximately 138-residue domain at the C-terminus of the a-macroglobulin subunit [1,2].

The crystal structure of the receptor binding domain of bovine a2-macroglobulin has been determined at a resolution of 1.9 A. The domain is primarily a nine-strand b structure with a jelly roll topology, but it also contains two small a helixes [3].

The surface patch responsible for receptor recognition is thought to involve residues located on one of the two a helices in the domain as well as two b strands. Located on this a helix are two lysine residues that are important for receptor binding [4]. The structure is very similar to the approximately 100-residue C-terminal domain of factor XIII, a transglutaminase from the blood coagulation system [5].

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