Figure 5.
Novel allosteric regulation of the TF exosite revealed by comparing the cryo-EM structure of TF/FVIIa/XK1/10H10 with the sTF/FVIIa crystal structure (3TH2). (A) Superposition of 3TH2 crystal structure of sTF/FVIIa with the cryo-EM map and model of TF/FVIIa/XK1, aligned via their TF components. Insets highlight conformational differences in the FVIIa GLA domain (left box) and the TF 4×Ser loop (right box). The color scheme for the cryo-EM map (mesh) and model is as follows: FVIIa, orange; TF, purple; and XK1, light sea green. For the 3TH2 crystal structure, FVIIa is shown in light gray and sTF in black/dark gray. The map is contoured at 0.1. For clarity, the 10H10 density was subtracted from the cryo-EM map and omitted from the model. (B-E) In the close-up views, the map is contoured at 0.145, and key interacting residues are shown as sticks and labeled, with carbon atoms colored by molecule, nitrogen in blue, and oxygen in red. (B) Close-up view focusing on the FVIIa and XK1 GLA domains within the alignment of TF/FVIIa/XK1 (cryo-EM structure) with the 3TH2 crystal structure. Arrows indicate the 4×Ser loop. (C) Close-up comparison of the positions of residues R36 of FVIIa and K165 of TF in the cryo-EM structure vs the sTF/FVIIa crystal structure, with the 4×Ser loop indicated by arrows. (D) Close-up view of the TF 4×Ser loop (arrows) and the XK1 GLA domain in the alignment between the cryo-EM structure and the sTF/FVIIa crystal structure. Note that the 4×Ser loop in the sTF/FVIIa crystal structure (but not the cryo-EM structure) sterically clashes with the cryo-EM density map of the XK1 GLA domain. FVIIa was omitted in this view for clarity. (E) Another close-up view of the region including the TF 4×Ser loop (arrows), highlighting interactions between TF residues S162 and S163 with FVIIa residue F31 and XK1 residues γ20 and T21.

Novel allosteric regulation of the TF exosite revealed by comparing the cryo-EM structure of TF/FVIIa/XK1/10H10 with the sTF/FVIIa crystal structure (3TH2). (A) Superposition of 3TH2 crystal structure of sTF/FVIIa with the cryo-EM map and model of TF/FVIIa/XK1, aligned via their TF components. Insets highlight conformational differences in the FVIIa GLA domain (left box) and the TF 4×Ser loop (right box). The color scheme for the cryo-EM map (mesh) and model is as follows: FVIIa, orange; TF, purple; and XK1, light sea green. For the 3TH2 crystal structure, FVIIa is shown in light gray and sTF in black/dark gray. The map is contoured at 0.1. For clarity, the 10H10 density was subtracted from the cryo-EM map and omitted from the model. (B-E) In the close-up views, the map is contoured at 0.145, and key interacting residues are shown as sticks and labeled, with carbon atoms colored by molecule, nitrogen in blue, and oxygen in red. (B) Close-up view focusing on the FVIIa and XK1 GLA domains within the alignment of TF/FVIIa/XK1 (cryo-EM structure) with the 3TH2 crystal structure. Arrows indicate the 4×Ser loop. (C) Close-up comparison of the positions of residues R36 of FVIIa and K165 of TF in the cryo-EM structure vs the sTF/FVIIa crystal structure, with the 4×Ser loop indicated by arrows. (D) Close-up view of the TF 4×Ser loop (arrows) and the XK1 GLA domain in the alignment between the cryo-EM structure and the sTF/FVIIa crystal structure. Note that the 4×Ser loop in the sTF/FVIIa crystal structure (but not the cryo-EM structure) sterically clashes with the cryo-EM density map of the XK1 GLA domain. FVIIa was omitted in this view for clarity. (E) Another close-up view of the region including the TF 4×Ser loop (arrows), highlighting interactions between TF residues S162 and S163 with FVIIa residue F31 and XK1 residues γ20 and T21.

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