Extended Data Fig. 5: Structural analysis of HalA.
From: A DNA-gated molecular guard controls bacterial Hailong anti-phage defence
a, Isolated HalA protomer showing regions involved in membrane interaction and formation of the ion channel (transmembrane domain α6-α10) and regions involved in ODA binding (pentapeptide repeat domain). b, Isolated HalA tetrameric ion channel region used for structural homolog comparison. c,d, Protein structural homology of HalA transmembrane domain against all entries in PDB showing the DALI Z score and FoldSeek E value of the top 130 and 1200 hits respectively. Entries with annotated ion channel activity are highlighted. e, HalA comparison to structurally related and well-characterized ion channel proteins, and corresponding PDB entry IDs are in parentheses. 2TM domain of HalA and ion channel proteins were used to highlight their structural similarities within the ion selectivity filter and transmembrane regions. Highlighted 2TM domains are shown as individual proteins next to the full structure, or overlayed altogether with HalA. f, Detailed view of HalA interacting residues required for oligomerization. g, Detailed view of the ion channel comparing the closed state (cryo-EM structure) and AlphaFold model of HalA. The AlphaFold model shows a wider conformation of the ion conduction pathway, suggestive of conformational rearrangements that would lead to an open state in the absence of ODA. h, Detailed view of HalA residues involved in recognition of ODA binding specificity. Sequence-specific interactions occur between HalA residues T83, T104, and T124 with base dA5; S141 and N143 with base dA3; and side-chains W26, K109, and F139 facilitate additional interactions that control selective ODA recognition and restrict guanine and pyrimidine base recognition.
