Extended Data Fig. 8: Additional env2-Cbl co-crystal structures.

a, Crystal structure of env2 in the apo state showing only the binding pocket nucleotides (left). Alignment of the binding pockets of env2-CNCbl (protomer A) and the apo state (right). In all structural representations, the binding pocket nucleotides G19 (yellow), A20 (green), and A68 (cyan) are colored and the β-axial is shown in magenta. All mesh representations correspond to a simulated annealing 2F_o-F_c map where A20 and the ligand (if present) were omitted from the model and are shown at 1 σ contour. b, Our env2-CNCbl co-crystal structure has two molecules in the asymmetric unit (ASU). Protomer A is already shown in Fig. 4c. Here, we are showing an alignment of the binding pockets of both protomers, which are nearly identical. c, Our env2-Cbl 4 co-crystal structure also has two molecules in the ASU. Protomer B is already shown in Fig. 4d. Here, we are showing an alignment of the binding pockets of both protomers, which reveals a different orientation of A20. This was a common feature of all but one of our co-crystal structures. In each protomer A, A20 is locked in a crystal lattice contact. In each protomer B, we get a variable conformation of A20, suggesting that A20 is dynamic. This also explains why the electron density of A20 is well defined in protomer A but less so in protomer B. We will therefore focus on the more solution-representative protomer B in all analyses. d, Co-crystal structure of env2-Cbl 5 showing only the binding pocket nucleotides and the β-axial group. e, Same as in d but for env2-Cbl 13. This structure had four molecules in the ASU. In all four protomers, there is well defined density for A20 and minimal conformational variety. f, Same as in d but for env2-Cbl 26. g, Same as in d but for env2-Cbl 33. h, Same as in d but for env2-Cbl 36. i, Same as in d but for env2-Cbl 37. j, Alignment of the binding pockets of protomers A (left) and B (right) for all the co-crystal structures shown here and in Fig. 4.