Editing Histone fold

{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox protein family
| Symbol = Histone
| Name = Histone fold
| image = 
| caption = 
| Pfam = 
| Pfam_clan = CL0012
| ECOD = 148.1.1
| InterPro = IPR009072
| SMART = 
| PROSITE = 
| MEROPS =
| CATH = 
| SCOP = 47112
| TCDB = 
| OPM protein = 
| CAZy = 
| CDD = cl45933
}}
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 [[heterodimer]]s, which subsequently assemble into a [[histone octamer]], playing a crucial role in the packaging of DNA into [[nucleosome]]s within [[chromatin]].<ref name="Baxevanis_1997" /> 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 (biology)|transcription]].<ref name = "Baxevanis_1997">{{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 }}</ref>

== Structure ==

The histone fold is typically around 70 [[amino acids]] long and is characterized by three [[alpha helices]] connected by two short, unstructured loops.<ref name = "Alva_2007">{{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 }}</ref> In the absence of DNA, core histones assemble into head-to-tail intermediates. For instance, [[Histone H3|H3]] and [[Histone H4|H4]] first form heterodimers, which then combine to form a tetramer. Similarly, [[Histone H2A|H2A]] and [[Histone H2B|H2B]] form heterodimers.<ref>{{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}}</ref> These interactions occur through hydrophobic "handshake" interactions between histone fold domains.<ref name=pmid7479959>{{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 }}</ref> 

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.<ref>{{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 }}</ref>

== Function ==

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}}

== 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. 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.<ref name = "Alva_2007" />

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.<ref name=pmid7479959/>

== References ==
{{Reflist}}

{{DEFAULTSORT:Histone Fold}}
[[Category:Protein folding]]
[[Category:Molecular biology]]
[[Category:Protein superfamilies]]