EXPRESSION AND DISULFIDE-BOND CONNECTIVITY OF THE 2ND LIGAND-BINDING REPEAT OF THE HUMAN LDL RECEPTOR

The human LDL receptor (LDLR) has a binding domain which consists of seven contiguous ligand-binding (LB) repeats, each similar to 40 amino acids long with three disulfide bonds, The second LB repeat, which is required for full binding of LDL, has been expressed, purified and folded to yield a single, fully oxidized isomer, By selective reduction and alkylation, we have shown that the cysteine residues have a I-III, II-V, IV-VI connectivity, matching that recently determined for the amino-terminal repeat, We suggest that the first two LB repeats of the LDLR, with their unique disulfide-bonding pattern, serve as a structural paradigm for other LS repeats.