The histone fold is a structural motif located near the C-terminus of histone proteins, characterized by three alpha helices separated by two loops. This motif facilitates the formation of heterodimers, which subsequently assemble into a histone octamer, playing a crucial role in the packaging of DNA into nucleosomes within chromatin.[1] This fold is an ancient and highly conserved structural motif, essential for DNA compaction and regulation across a wide range of species.
| Histone fold | |
|---|---|
| Identifiers | |
| Symbol | Histone |
| Pfam clan | CL0012 |
| ECOD | 148.1.1 |
| InterPro | IPR009072 |
| SCOP2 | 47112 / SCOPe / SUPFAM |
| CDD | cl45933 |
Discovery
editThe histone fold motif was first discovered in TATA box-binding protein-associated factors, which play a key role in transcription.[1]
Structure
editThe histone fold is typically around 70 amino acids long and is characterized by three alpha helices connected by two short, unstructured loops.[2] 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.[3] These interactions occur through hydrophobic "handshake" interactions between histone fold domains.[4]
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.[5]
Function
editThe histone fold plays a crucial role in nucleosome formation by mediating interactions between histones. The largest interface surfaces are found in the heterotypic dimer interactions of H3-H4 and H2A-H2B. These interactions are primarily mediated by the "handshake" motif between histone fold domains. Additionally, the H2A structure has a unique loop modification at its interface, contributing to its distinct role in transcriptional activation.[citation needed]
Evolution
editThe 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. Notably, archaeal single-chain histones, similar to eukaryotic histones, are found in the bacterium Aquifex aeolicus, suggesting a shared ancestry between eukaryotes and archaea, with possible lateral gene transfers to bacteria.[2]
Studies on species like Drosophila have revealed variations in the histone fold motif, particularly in the subunits of transcription initiation factors. These proteins contain histone-like structures, which show that the histone fold motif can also be found in non-histone proteins involved in protein-protein and protein-DNA interactions.[4]
References
edit- ^ a b Baxevanis AD, Landsman D (January 1997). "Histone and histone fold sequences and structures: a database". Nucleic Acids Research. 25 (1): 272–273. doi:10.1093/nar/25.1.272. PMC 146383. PMID 9016552.
- ^ a b Alva V, Ammelburg M, Söding J, Lupas AN (March 2007). "On the origin of the histone fold". BMC Structural Biology. 7 (1): 17. doi:10.1186/1472-6807-7-17. PMC 1847821. PMID 17391511.
- ^ Watson JD, Baker TA, Bell SP, Gann A, Levine MK, Losick R (2008). Molecular Biology of the Gene. Pearson/Benjamin Cummings. ISBN 978-0-8053-9592-1.[page needed]
- ^ a b Arents G, Moudrianakis EN (November 1995). "The histone fold: a ubiquitous architectural motif utilized in DNA compaction and protein dimerization". Proceedings of the National Academy of Sciences of the United States of America. 92 (24): 11170–11174. Bibcode:1995PNAS...9211170A. doi:10.1073/pnas.92.24.11170. PMC 40593. PMID 7479959.
- ^ Mariño-Ramírez L, Kann MG, Shoemaker BA, Landsman D (October 2005). "Histone structure and nucleosome stability". Expert Review of Proteomics. 2 (5): 719–729. doi:10.1586/14789450.2.5.719. PMC 1831843. PMID 16209651.