The histone fold is a structural motif located near the C-terminus of histone proteins (H2/H3/H4), characterized by three alpha helices separated by two loops. This motif facilitates the formation of histone heterodimers, which subsequently assemble into a histone octamer, playing a crucial role in the packaging of DNA into nucleosomes within chromatin.
Structure
The histone fold is typically around 70 amino acids long and is characterized by three alpha helices connected by two short, unstructured loops. In the absence of DNA, core histones assemble into head-to-tail intermediates. For instance, H3 and H4 first form heterodimers, which then combine to form a tetramer. Similarly, H2A and H2B form heterodimers. These interactions occur through hydrophobic "handshake" interactions between histone fold domains.
Histones H4 and H2A can form internucleosomal contacts that, when acetylated, enable ionic interactions between peptides. These interactions can alter the surrounding internucleosomal contacts, leading to chromatin opening and increased accessibility for transcription.
Function
The histone fold is a multifunctional domain. It is found in both histones and non-histone transcription factors. It serves a wide range of related functions including protein-DNA binding and protein dimerization.
Evolution
The histone fold is thought to have evolved from ancestral peptide sets that formed helix-strand-helix motifs. These peptides are believed to have originated from ancient fragments, which may be precursors to the modern H3-H4 tetramer found in eukaryotes. Archaea possess single-chain histones with a similar DNA-packaging function, suggesting a shared ancestry between eukaryotes and archaea. One bacterium, Aquifex aeolicus, also has one archaeal-type histone gene from later horizontal gene transfer. Only 1.86% of bacteria genomes surveyed in 2023 contain a histone-fold protein, compared to 92.8% of genomes that encode HU (histone-like DNA-binding protein).
See also
- Double histone fold