Structural basis for C. elegans pairing center DNA binding specificity by the ZIM/HIM-8 family proteins

Nat Commun. 2024 Nov 28;15(1):10355. doi: 10.1038/s41467-024-54548-9.

Abstract

Pairing center (PC) on each chromosome of Caenorhabditis elegans is crucial for homolog pairing and initiating synapsis. Within each PC, clusters of 11/12 bp DNA motif recruit one of four paralogous meiosis-specific proteins: ZIM-1, ZIM-2, ZIM-3, or HIM-8. However, the mechanistic basis underlying the specificity of ZIM/HIM-8-PC DNA interaction remains elusive. Here, we describe crystal structures of HIM-8, ZIM-1 and ZIM-2 DNA binding domains (ZF1, ZF2 and CTD) in complex with their cognate PC DNA motifs, respectively. These structures demonstrated the ZF1-2-CTD folds as an integrated structural unit crucial for its DNA binding specificity. Base-specific DNA-contacting residues are exclusively distributed on ZF1-2 and highly conserved. Furthermore, the CTD potentially contributes to the conformational diversity of ZF1-2, imparting binding specificity to distinct PC DNA motifs. These findings shed light on the mechanism governing PC DNA motif recognition by ZIM/HIM-8 proteins, suggesting a co-evolution relationship between PC DNA motifs and ZF1-2-CTD in shaping the specific recognition.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Caenorhabditis elegans Proteins* / chemistry
  • Caenorhabditis elegans Proteins* / genetics
  • Caenorhabditis elegans Proteins* / metabolism
  • Caenorhabditis elegans* / genetics
  • Caenorhabditis elegans* / metabolism
  • Cell Cycle Proteins
  • Chromosome Pairing
  • Crystallography, X-Ray
  • DNA / chemistry
  • DNA / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Models, Molecular
  • Nucleotide Motifs
  • Protein Binding*
  • Protein Domains

Substances

  • Caenorhabditis elegans Proteins
  • HIM-8 protein, C elegans
  • DNA-Binding Proteins
  • DNA
  • Cell Cycle Proteins