histone fold

The histone fold motif was first discovered in TATA box-binding protein-associated factors, which play a key role in transcription.{{cite journal | vauthors = Baxevanis AD, Landsman D | title = Histone and histone fold sequences and structures: a database | journal = Nucleic Acids Research | volume = 25 | issue = 1 | pages = 272–273 | date = January 1997 | pmid = 9016552 | pmc = 146383 | doi = 10.1093/nar/25.1.272 | doi-access = free }}

The histone fold is typically around 70 amino acids long and is characterized by three alpha helices connected by two short, unstructured loops.{{cite journal | vauthors = Alva V, Ammelburg M, Söding J, Lupas AN | title = On the origin of the histone fold | journal = BMC Structural Biology | volume = 7 | issue = 1 | pages = 17 | date = March 2007 | pmid = 17391511 | pmc = 1847821 | doi = 10.1186/1472-6807-7-17 | doi-access = free }} 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.{{cite book | vauthors = Watson JD, Baker TA, Bell SP, Gann A, Levine MK, Losick R |title=Molecular Biology of the Gene |date=2008 |publisher=Pearson/Benjamin Cummings |isbn=978-0-8053-9592-1 }}{{page needed|date=July 2020}} These interactions occur through hydrophobic "handshake" interactions between histone fold domains.{{cite journal | vauthors = Arents G, Moudrianakis EN | title = The histone fold: a ubiquitous architectural motif utilized in DNA compaction and protein dimerization | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 92 | issue = 24 | pages = 11170–11174 | date = November 1995 | pmid = 7479959 | pmc = 40593 | doi = 10.1073/pnas.92.24.11170 | doi-access = free | bibcode = 1995PNAS...9211170A }}

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.{{cite journal | vauthors = Mariño-Ramírez L, Kann MG, Shoemaker BA, Landsman D | title = Histone structure and nucleosome stability | journal = Expert Review of Proteomics | volume = 2 | issue = 5 | pages = 719–729 | date = October 2005 | pmid = 16209651 | pmc = 1831843 | doi = 10.1586/14789450.2.5.719 }}

The 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|date=July 2020}}

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. 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.

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.

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Category:Protein folding

Category:Molecular biology

Category:Protein superfamilies