FIGURE 6.

Upper panel, sequence alignment of LA3-LA6 of VLDLR with LA2-LA5 of LDLR. The possible apoE-binding residues in each LA module are shaded yellow for Asp/Glu/Asn/Gln and green for Trp/Phe. The Ca²⁺-binding residues are shaded light blue and underlined. Residues that use backbone carbonyl to chelate Ca²⁺ are labeled with italic letters for the one-letter code of the amino acid of these residues. Residues that bind to both apoE-NT and Ca²⁺ are underlined and shaded based on apoE binding. LA3 and LA5 of VLDLR contain a typical consensus sequence for ligand binding (WXCDX(D/E)XDC), whereas LA4 has the sequence FXCNXQXDC. (Boldface letters are residues involved in the interaction with the ligand.) Lower panels, docking model for apoE-NT binding to LA3-LA5 of VLDLR. Lower left, overview of this docking model. Both apoE-NT and LA3-LA5 of VLDLR are rendered as ribbons, with the side chain of the binding residues (Lys/Arg in apoE-NT and Asp/Glu/Asn/Gln/Trp/Phe in LA3-LA5 of VLDLR) shown as sticks. The helix bundle of apoE-NT is colored purple, and the major receptor-binding region (residues 136-150) and helices N and C are colored green. For LA3-LA5 of VLDLR: LA3, light blue; LA4, light orange; LA5, gray. Insets A, B, and C is the lower left panel show the interaction regions of apoE and the receptor. The insets are zoomed and displayed in the right panels. Lower right, A, binding interface between Lys-143/Lys-146 of apoE-NT and Asp-135/Glu-137/Asp-139/Trp-132/Gly-136 of LA3 of VLDLR. B, possible binding interface between Lys-1/Lys-3 of apoE-NT and Asn-174/Gln-176/Glu-178/Phe-171 of LA4 of VLDLR. C, binding interface between Arg-172/Arg-178 of apoE-NT and Asp-213/Asp-215/Asp-217/Trp-210 of LA5. The side chain carbons in apoE-NT, brown sticks; side chain carbon in LA modules, pink sticks; side chain nitrogen, blue stick; oxygen, red stick; side chain hydrogen, green stick. The salt bridges are indicated by dashed blue lines, and H-bonds are shown by dashed red lines.