Activity, disulphate mapping and structural modelling of the fifth domain of human β2‐glycoprotein I

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Abstract
Complexes formed by the interaction of negatively charged phospholipids and β2-glycoprotein I(β2-I) are the target of autoantibodies in systemic lupus erythematosus. The highly positively charged fifth (C-terminal) domain of human β2-I was produced as a fusion protein in an Escherichia coli expression system and was shown to bind to the negatively charged phospholipid, cardiolipin, almost as well as the intact protein. In an attempt to define the 3D structure of this domain, the disulphate linkage pattern was determined and shown to be Cys 1–4, Cys 2–5 and Cys 3–6 in contradiction to an earlier report. In the light of this information, the sequence of the fifth domain of β2I(β2-I-5) is readily aligned with that of the 16th repeat of factor H, of which the 3D structure is known, and a model of β2I-5 has been built by homology. On the basis of the model we suggest residues that might be the target of profitable site-directed mutagenesis in structure—function studies.