(A) Human α6 ring viewed along the three-fold (triangle) and two-fold (oval) symmetry axes. Dashed box in middle panel highlights cone domain interactions detailed in panel C. Insets show density (grey) and atomic model for a three strand segment of the catalytic core β-barrel (residues Phe297-Leu301, Leu328-Ile334, Tyr404-Tyr407) and two helices (residues Ile228-Ser244) that pair at the α dimer interface. Regions of the structure are colored as in Figure 1 with alternating subunits in faded colors. dATP densities in yellow. (B) Cone domain in the human α6 ring structure is ~20° away from its position in the human α2 crystal structure colored tan (PDB: 3HNC). The gray rod indicates the rotation axis. (C) Cone domain viewed along the two-fold symmetry axis (oval) and an orthogonal view showing contacting residues, which are mostly hydrophobic. (D) dATP in the cone domain of the cryo-EM structure makes hydrogen bonds through its base, sugar, and phosphates indicated by dashed lines. Nucleotide density is shown in yellow mesh with dATP carbon yellow, oxygen red, phosphorus gold, and nitrogen blue. (E) The dATP-inhibited α4β4 ring of E. coli (PDB: 5CNS) uses the same face (helices 1 and 2) of the cone domain to contact the β subunit (orange). For comparison, the cone domain of E. coli α is oriented as in panel (C).