Fig. 1: Comparative analysis of prokaryotic histones composed exclusively of histone fold domains.

a Cluster map of ~3300 prokaryotic histones containing only the histone fold domain. Each dot represents a single protein sequence, edges reflect pairwise sequence similarity. Structures of representative proteins—either crystal structures (PDB IDs in parentheses) or AlphaFold models—are shown in cartoon representation. AlphaFold models are colored by pLDDT confidence scores. Representative proteins include: HstA from Haloferax volcanii (D4GS56), an archaeal nucleosomal-like pseudodimeric histone; HMfB from Methanothermus fervidus (P19267), an archaeal nucleosomal histone; HBb from Bdellovibrio bacteriovorus (Q6MRM1), a bacterial dimeric histone; HLp from Leptospira perolatii (A0A2M9ZN55), a bacterial FtF histone; HTkC from Thermococcus kodakarensis (Q5JDW7), an archaeal FtF histone; and Q5JHD0 from T. kodakarensis (Q5JHD0) and AQ328 from Aquifex aeolicus (O66665), both prokaryotic pseudodimeric histones. b Multiple sequence alignment of representative histones from both eukaryotes and prokaryotes, including Homo sapiens (H2A: P04908; H2B: P62807; H3: P68431; H4: P62805), M. fervidus (HMfA: P48781; HMfB: P19267), H. volcanii (HstA: D4GS56), B. bacteriovorus (HBb: Q6MRM1), Hymenobacter marinus (NCBI accession No.: ATH09486), Waddlia chondrophila (D6YWW1), Simkania negevensis (F8L7X8), L. perolatii (HLp: A0A2M9ZN55), L. interrogans (Q8F3E8), Leptonema illini (H2CFS2), T. kodakarensis (HTkC: Q5JDW7), H. volcanii (D4GZE0), Candidatus Heimdallarchaeum endolithica (A0A9Y1FPJ9), A. aeolicus (O66665), and Methanocaldococcus jannaschii (A0A832T4V6). α-helices are annotated with “h” based on crystal structures of H2A, HMfA, HBb, HLp, and AQ328. Conserved residues associated with DNA binding and oligomerization are highlighted in green and yellow, respectively. HLp residues contributing to tetramerization in the HLp crystal structure (PDB: 9QT0) are underlined, while those interacting with the DNA backbone in HLp-DNA complexes (PDB: 9QT1 and 9QT2) are shown in bold. Unless otherwise stated, accession numbers in parentheses refer to UniProtKB.