Assembly and Architecture of the EBV B Cell Entry Triggering Complex
Figure 5
The pseudoatomic model of the triggering complex places the gp42 HP in contact with gH.
(A) Pseudo-atomic model of the gHgL/gp42/HLA-DQ2 complex obtained from the EM envelope fitting. The individual domains of each protein are marked and the hydrophobic pocket (HP) in gp42 is highlighted with an arrow. The C-termini of gH and HLA chains are similarly marked and lie on one side of the complex at ∼70 Å of each other. (B) The gp42 HP interaction site with gHgL. Two sides of the gp42 HP interact with gH between D-II and D-III, including a loop between helices 2α-6 and 2α-7 from D-II and helix 3α-9 from D-III. Residues that have been previously mutated in the gp42 HP [30] are indicated, H206 and T193 that had linker insertions as Cα spheres (dark blue) and F210 as sticks (dark blue) within the hydrophobic pocket (light blue Cα spheres) as defined in [27], [28], which disrupt membrane fusion activity. I159 is also shown as sticks (light blue). The gp42 HP faces away from the observer in this orientation. The gp42 interaction with the HLA-class II β-chain (orange) brings gH and HLA into close proximity. Residue C114 which is the only unpaired cysteine in wt gp42 is shown as sticks (light blue) (C) Close-up view of gp42 residue I159 (blue), located in the gp42 158 loop [28], at the junction of the HLA and gH contact sites. The locations of gH mutant residues that were tested are indicated, including G276 (cyan) in the 2α-6/2α-7 loop (D-II) and D511 and S507 in the 3α- helix 9 (D-III). The view is rotated 180° along vertical axis and then rotated 45° counter-clockwise with the horizontal axis compared to the orientation shown in (A) and (B). Images were rendered using MacPyMol [55].