C2H2type

C2H2-type refers to a class of zinc finger protein motifs that function as DNA-binding domains in many eukaryotic transcription factors. The name comes from the zinc coordination geometry: two cysteine residues and two histidine residues bind a zinc ion, stabilizing the finger structure.

Structure and arrangement

A single C2H2 finger is typically about 28 to 30 amino acids long and folds into a beta-hairpin followed by an alpha-helix. The canonical zinc coordination motif is Cys-X2-4-Cys-X12-His-X3-4-His, with the cysteines and histidines providing ligands to the zinc ion. The recognition helix of the finger inserts into the DNA major groove, and specific amino acid residues on this helix contact the DNA bases, determining binding specificity. Proteins often contain arrays of multiple C2H2 fingers linked by short spacers, allowing recognition of longer DNA sequences.

Function and distribution

C2H2-type zinc finger domains are the most common DNA-binding motifs in animals and are also found in plants and fungi. They occur in many transcription factors, including Krüppel-like factors and ZNF (zinc-finger) protein families. The modular nature of the finger repeats enables proteins to recognize diverse DNA sequences; duplications and shuffling of finger modules contribute to evolutionary diversification of gene regulation.

Variations and notes

While the classic motif is Cys-X2-4-Cys-X12-His-X3-4-His, spacing and residues can vary, and plant C2H2 fingers often contain distinctive motifs such as QALGGH. It is distinct from acetylene (C2H2) chemistry and from other zinc finger types like C4. C2H2-type domains are central to many regulatory networks governing development, differentiation, and response to environmental cues.