Biology:Histone fold
| Histone fold | |
|---|---|
| Identifiers | |
| Symbol | Histone |
| Pfam clan | CL0012 |
| InterPro | IPR009072 |
| SCOP2 | 47112 / SCOPe / SUPFAM |
| CDD | cl45933 |
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.[1] This fold is an ancient and highly conserved structural motif, essential for DNA compaction and regulation across a wide range of species.
Discovery
The histone fold motif was first discovered in TATA box-binding protein-associated factors, which play a key role in transcription.[1]
Structure
The 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
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.[4] Non-histone examples include CBF/NF-Y, TBP-associated factors (TAFs), the TBP/TATA-binding negative cofactor 2 (NC2α/β), and the CHRAC15/CHRAC17 subunits of the nucleosome remodeling complex CHRAC.[6]
Histones
CBF/NF-Y
The nuclear transcription factor Y (NF-Y) also known as the CCAAT-binding factor (CBF) is a transcriptional factor highly conserved among eukaryotes (including humans). It is a heterotrimer composed of NFYA, NFYB, and NFYC. NFYA has a sequence-specific, non-histone-fold DNA-binding domain, while NFYB and NFYC both have a non-sequence-specific histone-fold DNA-binding domain. NFYB and NFYC form a structure similar to H2A/H2B.[6]
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.[2]
Expansion of bacterial genomic data has identified many other histone-fold proteins. The Bd0055 of Bdellovibrio bacteriovorus exhibits two unconventional (compared to eukaryotic and archaeal histone) modes of DNA-binding. The HLp of Leptospira perolatii is comparatively more conventional.[7] 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).[8]
References
- ↑ 1.0 1.1 "Histone and histone fold sequences and structures: a database". Nucleic Acids Research 25 (1): 272–273. January 1997. doi:10.1093/nar/25.1.272. PMID 9016552.
- ↑ 2.0 2.1 "On the origin of the histone fold". BMC Structural Biology 7 (1). March 2007. doi:10.1186/1472-6807-7-17. PMID 17391511.
- ↑ Molecular Biology of the Gene. Pearson/Benjamin Cummings. 2008. ISBN 978-0-8053-9592-1.
- ↑ 4.0 4.1 "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. November 1995. doi:10.1073/pnas.92.24.11170. PMID 7479959. Bibcode: 1995PNAS...9211170A.
- ↑ "Histone structure and nucleosome stability". Expert Review of Proteomics 2 (5): 719–729. October 2005. doi:10.1586/14789450.2.5.719. PMID 16209651.
- ↑ 6.0 6.1 Oldfield, Andrew J.; Henriques, Telmo; Kumar, Dhirendra; Burkholder, Adam B.; Cinghu, Senthilkumar; Paulet, Damien; Bennett, Brian D.; Yang, Pengyi et al. (11 July 2019). "NF-Y controls fidelity of transcription initiation at gene promoters through maintenance of the nucleosome-depleted region". Nature Communications 10 (1). doi:10.1038/s41467-019-10905-7.
- ↑ "PDB101: Molecule of the Month: Histones Across the Tree of Life". https://pdb101.rcsb.org/motm/314.
- ↑ Hocher, A; Laursen, SP; Radford, P; Tyson, J; Lambert, C; Stevens, KM; Montoya, A; Shliaha, PV et al. (November 2023). "Histones with an unconventional DNA-binding mode in vitro are major chromatin constituents in the bacterium Bdellovibrio bacteriovorus.". Nature microbiology 8 (11): 2006-2019. doi:10.1038/s41564-023-01492-x. PMID 37814071.
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