Extended Data Figure 5. hAptx RNA-DNA interactions.

a, Structural distortions of the hAptx bound RNA-DNA. A cartoon representation of the duplex from the hAptx/RNA-DNA/AMP/Zn reaction product complex (magenta and green) is shown superimposed on an ideal B-form DNA duplex (gray), showing distortion of the 5′-terminal nucleotides from B-form geometry. b, Electrostatic potential representation of the hAptx HIT-Znf DNA interaction interface is displayed with electropositive (blue) electronegative (red) and hydrophobic (white) surfaces. An extended positively charged surface of the Znf mediates sequence non-specific RNA-DNA contacts. Hydrophobic base stacking stabilizes the exposed ribonucleotide base. c, Trp167 and Tyr195 anchor the terminal ribonucleotide (green), and envelop the adenylate lesion (yellow). An omit σ-A weighted 1.95 Å Fo-Fc map is displayed contoured at 3.0 σ overlaid upon the AMP and RNA-DNA duplex product complex. The RNA-DNA duplex and AMP were excluded from the model for electron density map calculation. d, hAptx protein RNA-DNA and AMP lesion binding contacts are displayed schematically. e, The HIT (tan) and Znf (blue) surfaces mold a contiguous RNA-DNA damage interacting surface. f, Molecular details of the Znf structure-specific DNA damage binding interface. DNA-protein contacts are mediated by four basic side chains (Lys 276, Lys277, His 278, Lys314) of Znf helicies α3 and α5. Additional sugar-phosphate backbone contacts from Pro 329 and Ile 328, as well as the electropositive helix-dipole of helix α6 also engage the undamaged strand. g, Zn-binding by the hAptx C₂H₂ zinc finger subdomain. The Zn is coordinated with tetrahedral geometry by four zinc binding residues (Cys319, Cys322, His335 and His339) and scaffolds folding of the Znf domain.