1. Structure of an LDLR-RAP Complex Reveals a General Mode for Ligand Recognition by Lipoprotein Receptors 
Carl Fisher, Natalia Beglova, Stephen C. Blacklow 
Molecular Cell 
Volume 22, Issue 2, Pages (April 2006)
DOI: /j.molcel
Copyright © 2006 Elsevier Inc. Terms and Conditions

2. Figure 1 Sequence Alignment and Structure Overview
(A) Alignment of the three domains of human RAP. D1 and D3 were structurally aligned and D2 and D3 were aligned with ClustalW. The helices of D3 are represented schematically above the sequence in blue, and the helices of D1 (PDB: 1LRE) are boxed in blue. Interface residues are boxed in red. Sequence conservation as defined by ClustalW is indicated below the sequences.
(B) Alignment of LA repeat pairs from the LDLR (LA3-4) and LRP-1 (CR5-6). Residues identical in both proteins are shaded gray. LDLR residues that form salt bridges or hydrogen bonds with RAP-D3 are boxed in red; aromatic residues in contact with the lysines of RAP-D3 are boxed in green. Residues that participate in calcium coordination via side chain and backbone interactions are denoted by filled and open arrows, respectively. The three aspartate residues of the acidic pocket (I, II, III), conserved cysteine residues (black dots), and secondary structure elements (red) are also identified.
(C) Overall structure of the LA3-4:RAP-D3 complex. The LA3-4 (red) and RAP-D3 (blue) polypeptide chains are illustrated as ribbons, and a transparent molecular surface of LA3-4 is shown in light gray. The calcium ions bound by LA3 and LA4 are shown as yellow spheres. Disulfide bonds in LA3-4 are rendered as sticks, with sulfur atoms colored orange.
Molecular Cell  , DOI: ( /j.molcel )
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3. Figure 2 Interface between LA3-4 and RAP-D3
(A and B) Electrostatic complementarity.
(A) Surface representation of LA3-4 colored by electrostatic surface potential, with a backbone ribbon trace of RAP-D3 illustrated in gray. The surface is colored on a sliding scale with regions of negative electrostatic potential in red (<−15 kT), regions of positive electrostatic potential (>15 kT) in blue, and neutral regions in white.
(B) Surface representation of RAP-D3 colored by electrostatic surface potential (as in [A]), with a backbone ribbon trace of LA3-4 in gray.
(C and D) Interactions between the LA acidic pockets and lysine residues of RAP-D3.
(C) Interactions between LA3 and K270 of RAP-D3.
(D) Interactions between LA4 and K256 of RAP-D3. LA module backbone traces are illustrated as crimson ribbons, and interacting side chains (carbon, salmon; oxygen, red) are rendered as sticks. The RAP-D3 polypeptide backbone is shown as a blue ribbon, with the lysine side chain (carbon, cyan; nitrogen, blue) in stick form. The calcium ions bound by LA3 (C) and LA4 (D) are shown as yellow spheres. Hydrogen bonds are shown as dashed black lines.
Molecular Cell  , DOI: ( /j.molcel )
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4. Figure 3
Comparison of the LA4:RAP-D3 Interface with Other LA Module Interfaces
Each panel represents a least-squares backbone superposition of the corresponding LA module over a 10-residue segment encompassing the aromatic residue and the acidic pocket. The LA4:RAP-D3 structure is rendered in gray.
(A) Comparison to the LA3:RAP-D3 interface (backbone, cyan ribbon).
(B) Comparison to the LDLR intramolecular interface (Rudenko et al., 2002) between LA4 and the YWTD β-propeller (backbone, magenta ribbon; PDB ID code, 1N7D).
(C) Comparison to the LDLR intramolecular interface between LA5 and the YWTD β-propeller (backbone, orange ribbon).
(D) Comparison to the interface (Verdaguer et al., 2004) between VLDLR repeat three and HRV2 (backbone, green ribbon; PDB ID code, 1V9U).
Molecular Cell  , DOI: ( /j.molcel )
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5. Figure 4 Docking Model for ApoE Binding
(A) Ribbon diagram of the receptor binding domain of apoE4 (ApoE-RBD; PDB ID code, 1GS9). Helix 4 is depicted in a darker shade of gold and two lysines implicated in LDLR binding (Zaiou et al., 2000) are labeled and rendered as sticks.
(B–D) Backbone superposition of residues 140–150 of ApoE-RBD onto residues 250–260 of RAP-D3 in the LA3-4:RAP-D3 structure. In (B) (overview) and (D) (detailed view around the RAP-D3:LA4 interface), ApoE is shown as a ribbon diagram, with lysine residues 143 and 146 highlighted as sticks. In (C), the molecular surface of ApoE-RBD is shown, colored according to vacuum surface electrostatic potential (red, <−70 kT; blue, >70 kT). In (D), helix three of RAP-D3 has been removed for clarity, and salt bridges from RAP-D3 to the aspartates (I-III) of LA4 are indicated with dashed lines.
Molecular Cell  , DOI: ( /j.molcel )
Copyright © 2006 Elsevier Inc. Terms and Conditions