Searching for New Z-DNA/Z-RNA Binding Proteins Based on Structural Similarity to Experimentally Validated Zα Domain

Int J Mol Sci. 2022 Jan 11;23(2):768. doi: 10.3390/ijms23020768.

Abstract

Z-DNA and Z-RNA are functionally important left-handed structures of nucleic acids, which play a significant role in several molecular and biological processes including DNA replication, gene expression regulation and viral nucleic acid sensing. Most proteins that have been proven to interact with Z-DNA/Z-RNA contain the so-called Zα domain, which is structurally well conserved. To date, only eight proteins with Zα domain have been described within a few organisms (including human, mouse, Danio rerio, Trypanosoma brucei and some viruses). Therefore, this paper aimed to search for new Z-DNA/Z-RNA binding proteins in the complete PDB structures database and from the AlphaFold2 protein models. A structure-based similarity search found 14 proteins with highly similar Zα domain structure in experimentally-defined proteins and 185 proteins with a putative Zα domain using the AlphaFold2 models. Structure-based alignment and molecular docking confirmed high functional conservation of amino acids involved in Z-DNA/Z-RNA, suggesting that Z-DNA/Z-RNA recognition may play an important role in a variety of cellular processes.

Keywords: Z-DNA; Z-RNA; Zα domain; bioinformatics; protein binding.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • DNA, Z-Form / chemistry*
  • DNA, Z-Form / metabolism
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism
  • Models, Molecular*
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Nucleic Acid Conformation
  • Protein Binding
  • Protein Conformation
  • Protein Interaction Domains and Motifs*
  • RNA / chemistry*
  • RNA / metabolism
  • RNA-Binding Proteins / chemistry*
  • RNA-Binding Proteins / metabolism
  • Structure-Activity Relationship

Substances

  • DNA, Z-Form
  • DNA-Binding Proteins
  • RNA-Binding Proteins
  • RNA