Autoreactivity and Exceptional CDR Plasticity (but Not Unusual Polyspecificity) Hinder Elicitation of the Anti-HIV Antibody 4E10
Figure 11
Structures of 4E10, b12, 2F5, the CL-binding yeast cytochrome bc1 complex and Annexin V.
(A) The structure of the Fv domain of 4E10 (from 2FX7.pdb [9]) is shown in a semi-transparent molecular surface representation colored by electrostatic potential (blue: positive; red: negative). Side-chains of key residues are shown in licorice-stick representations and labeled. In this orientation, the VL domain is in the upper left and the VH domain is in the lower right. The backbone of the epitope peptide co-crystallized in this structure is shown in a cartoon representation, with side-chains shown in licorice-stick representations colored by atom-type (carbon: gray; oxygen: red; nitrogen: blue). (B) The molecular surfaces of the Fv domains of 4E10 (top) and 2F5 (bottom) are shown, oriented with VL domains at left and the VH domains at right. The surface is colored to show hydrophobic patches, defined by the program HotPatch [113]; patches are colored in descending order of total area (red, orange, yellow …). Key residues and hydrophobic patch areas are indicated. (C) The structure of the Fv domain of b12 (from 3RU8.pdb [104]) is shown as in (A). (D) Annexin V (1A8A.pdb [114]) is shown as a semi-transparent molecular surface colored by underlying atom type, highlighting the exposed tryptophan side-chain (shown in licorice-stick representation). Calcium ions, shown as green spheres, coordinate the phosphate moiety from PS (shown in a licorice-stick representation, colored by atom-type as in (A) plus phosphorus in orange). (E) The structure of the unbound form of 4E10 (4LLV.pdb) is shown as a semi-transparent molecular surface representation colored as in (A). Side-chains of key residues are shown in licorice-stick representations and labeled. The view of the molecule has been rotated roughly 45° from the orientation of 4E10 shown in (A). The coordinated SO4 ion is shown in a licorice-stick representation colored by atom type as in (A) plus sulfur in yellow. (F) CL is shown docked onto the unbound structure of 4E10 oriented and colored as in (E). Molecular images were generated with MacPyMOL [109].