Fig. 2: Overall structure of HIM-8 ZF1-2-CTD in complex with X chromosome PC DNA.

a Overview of the ZF1-2-CTD complex of HIM-8 in association with the 12-bp X chromosome PC motif. ZF1, ZF2, and CTD are depicted in aquamarine, light blue, and light pink, respectively. The top and bottom strands of the motif are colored salmon and gray, respectively. b Sequence alignment of HIM-8 ZF1, HIM-8 ZF2, Zif268 ZF1, and TZAP ZF11. Secondary structural elements of HIM-8 ZF1 (top panel) and the other three (bottom panel) are presented. Cysteine and histidine residues crucial for zinc atom binding are highlighted in cyan. Three residues in classical C2H2 zinc fingers that interact specifically with DNA bases are marked as positions −1, −4, and −7. “C.elegans” was abbreviated as “Ce”, “mouse” was abbreviated as “mm”, “human” was abbreviated as “hs”. c Schematic representation illustrating the HIM-8 ZF1-2-CTD structure. ZF1 comprises a ββηα structure, ZF2 includes a ββα configuration, and CTD contains an ηαη arrangement. CTD folds back and tightly associates with ZF1 and ZF2. d Structural comparison between HIM-8 ZF1 and TZAP ZF11 using TM-align, resulting in a root-mean-square deviation (RMSD) of 1.84 Å and a TM-score of 0.47. e Structural alignment of HIM-8 ZF2 and TZAP ZF11 using TM-align, resulting in an RMSD of 1.30 Å and a TM-score of 0.74. f Hydrophobic contacts and hydrogen-bond interactions at the ZF1-2 and CTD interface are illustrated. This plot was generated using LigPlot+ v. 2.2.8. Residues above the black dashed line belong to the CTD, while those below are part of the ZF1-2 domain. g A comparison of the HIM-8 ZF1-2-CTD crystal structure (blue) with its predicted counterpart from AlphaFold 3 (red) reveals an RMSD of 1.048 Å. h, i The crystal structure of the HIM-8 ZF1-2-CTD complexed with the 12-bp X chromosome PC dsDNA motif (blue) is compared to the predicted protein-DNA complex structure from AF3 (red) via the DNA alignment (h) and via the protein alignment (i), respectively.