Histone fold

Last updated March 23, 2024

A histone fold is a structurally conserved motif found near the C-terminus in every core histone sequence in a histone octamer responsible for the binding of histones into heterodimers.

The histone fold averages about 70 amino acids and consists of three alpha helices connected by two short, unstructured loops.^[1] When not in the presence of DNA, the core histones assemble into head-to-tail intermediates (H3 and H4 first assemble into heterodimers then fuse two heterodimers to form a tetramer, while H2A and H2B form heterodimers^[2]) via extensive hydrophobic interactions between each histone fold domain in a "handshake motif".^[3] Also the histone fold was first found in TATA box-binding protein-associated factors, which is a main component in transcription.

The histone fold's evolution can be found by different combinations of ancestral sets of peptides that make up helix-strand-helix motif that come from the three folds from the ancestral fragments. These peptide chains can be found in the archaeal histones, which could have come from eukaryotic H3-H4 tetramer. The archaeal single-chain histones are also found in the bacterium Aquifex aeolicus. Which helps the diverse bacteria phylogeny coming from the ancestry of eukaryotes and archaea with lateral gene transfers to get to the bacteria.^[4] These lead into the octamer articulated protein endoskeleton for DNA compaction. From this endoskeleton it has a central segment that folds for the histone dimerization. This then leads into the end segments of the fold to make properties of dimer-dimer contacts that also cap the protein super helix at the octamer.

One species that looked at is Drosophila, and in the subunits of the Drosophila transcription initiation factor has specific amino acid sequences that have different characteristics of the histone folds that make up the two proteins make up the subunits.^[3] When just looking at the histone fold motif in the Drosophila the protein-protein and the protein DNA interaction of the core histone proteins can be found by looking at the non-histone proteins. This can then be used in “Structural studies on the TAFII42/TAFII62 complex from Drosophila and HMfB from Methanococcus fervidus, proteins identified as containing the histone fold in the aforementioned searches, confirmed that a histone-like substructure exists in these proteins, with the individual proteins folding into the canonical histone fold motif”.^[5] The evolutionary structure and range of the histone protein-protein and DNA-protein interactions of the histone fold proteins has a very wide range of evolutionary traits that form the structures and other proteins.

Histone folds play a role in the nucleosomal core particle by conserving histone interactions when looking at interface surfaces. These contain more than one histone fold. The structure of the nucleosome core particle has two modes that have the largest interaction surfaces with are in groups H3-H4 and H2A-H2B heterotypic dimer interactions. When looking at the H2A-H2A structure it has a modification of the loop at the interface that excludes it from clustering with the same interface of other structures. Which makes it have a different function in the transcriptional activation. Also the two modes are distinct due to having the longest helix chains. These use the handshake interactions between the two histone folds, while they also use it to make themselves unique comparted to the rest of the modes. Similarly modes 5 and 7 of the core nucleosome particle use two types of histone fold dimers which show that all histone domains share a similar structural motif to be able to be able to interact with one another and to interact in different ways. Showing how flexible and adaptive the structure of histones are.^{[ citation needed ]}

H4 and H2A can form an internucleosomal contacts that can be acetylated to be able to perform ionic interactions between two peptides, which in turn could change the surrounding internucleosomal contacts that can make a way to opening the chromatin.^[6]

Related Research Articles

In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei and in most Archaeal phyla. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn are wrapped into 30-nanometer fibers that form tightly packed chromatin. Histones prevent DNA from becoming tangled and protect it from DNA damage. In addition, histones play important roles in gene regulation and DNA replication. Without histones, unwound DNA in chromosomes would be very long. For example, each human cell has about 1.8 meters of DNA if completely stretched out; however, when wound about histones, this length is reduced to about 90 micrometers (0.09 mm) of 30 nm diameter chromatin fibers.

A nucleosome is the basic structural unit of DNA packaging in eukaryotes. The structure of a nucleosome consists of a segment of DNA wound around eight histone proteins and resembles thread wrapped around a spool. The nucleosome is the fundamental subunit of chromatin. Each nucleosome is composed of a little less than two turns of DNA wrapped around a set of eight proteins called histones, which are known as a histone octamer. Each histone octamer is composed of two copies each of the histone proteins H2A, H2B, H3, and H4.

In molecular biology, a histone octamer is the eight-protein complex found at the center of a nucleosome core particle. It consists of two copies of each of the four core histone proteins. The octamer assembles when a tetramer, containing two copies of H3 and two of H4, complexes with two H2A/H2B dimers. Each histone has both an N-terminal tail and a C-terminal histone-fold. Each of these key components interacts with DNA in its own way through a series of weak interactions, including hydrogen bonds and salt bridges. These interactions keep the DNA and the histone octamer loosely associated, and ultimately allow the two to re-position or to separate entirely.

Histone H4 is one of the five main histone proteins involved in the structure of chromatin in eukaryotic cells. Featuring a main globular domain and a long N-terminal tail, H4 is involved with the structure of the nucleosome of the 'beads on a string' organization. Histone proteins are highly post-translationally modified. Covalently bonded modifications include acetylation and methylation of the N-terminal tails. These modifications may alter expression of genes located on DNA associated with its parent histone octamer. Histone H4 is an important protein in the structure and function of chromatin, where its sequence variants and variable modification states are thought to play a role in the dynamic and long term regulation of genes.

Histone H2A is one of the five main histone proteins involved in the structure of chromatin in eukaryotic cells.

Histone H2B is one of the 5 main histone proteins involved in the structure of chromatin in eukaryotic cells. Featuring a main globular domain and long N-terminal and C-terminal tails, H2B is involved with the structure of the nucleosomes.

Eukaryotic chromosome structure refers to the levels of packaging from raw DNA molecules to the chromosomal structures seen during metaphase in mitosis or meiosis. Chromosomes contain long strands of DNA containing genetic information. Compared to prokaryotic chromosomes, eukaryotic chromosomes are much larger in size and are linear chromosomes. Eukaryotic chromosomes are also stored in the cell nucleus, while chromosomes of prokaryotic cells are not stored in a nucleus. Eukaryotic chromosomes require a higher level of packaging to condense the DNA molecules into the cell nucleus because of the larger amount of DNA. This level of packaging includes the wrapping of DNA around proteins called histones in order to form condensed nucleosomes.

The solenoid structure of chromatin is a model for the structure of the 30 nm fibre. It is a secondary chromatin structure which helps to package eukaryotic DNA into the nucleus.

Histone H2B type 2-E is a protein that in humans is encoded by the HIST2H2BE gene.

Histone H2A type 1-B/E is a protein that in humans is encoded by the HIST1H2AE gene.

Histone H2A type 1-H is a protein that in humans is encoded by the HIST1H2AH gene.

Histone H2A type 3 is a protein that in humans is encoded by the HIST3H2A gene.

Histone H2A type 1-A is a protein that in humans is encoded by the HIST1H2AA gene.

Histone H2A type 2-B is a protein that in humans is encoded by the HIST2H2AB gene.

FACT is a heterodimeric protein complex that affects eukaryotic RNA polymerase II transcription elongation both in vitro and in vivo. It was discovered in 1998 as a factor purified from human cells that was essential for productive, in vitro Pol II transcription on a chromatinized DNA template.

Histone H2A.J is a protein that in humans is encoded by the H2AFJ gene.

Histone H2A-Bbd type 2/3 also known as H2A Barr body-deficient is a histone protein that in humans is encoded by the H2AFB2 gene.

Nucleic acidquaternary structure refers to the interactions between separate nucleic acid molecules, or between nucleic acid molecules and proteins. The concept is analogous to protein quaternary structure, but as the analogy is not perfect, the term is used to refer to a number of different concepts in nucleic acids and is less commonly encountered. Similarly other biomolecules such as proteins, nucleic acids have four levels of structural arrangement: primary, secondary, tertiary, and quaternary structure. Primary structure is the linear sequence of nucleotides, secondary structure involves small local folding motifs, and tertiary structure is the 3D folded shape of nucleic acid molecule. In general, quaternary structure refers to 3D interactions between multiple subunits. In the case of nucleic acids, quaternary structure refers to interactions between multiple nucleic acid molecules or between nucleic acids and proteins. Nucleic acid quaternary structure is important for understanding DNA, RNA, and gene expression because quaternary structure can impact function. For example, when DNA is packed into heterochromatin, therefore exhibiting a type of quaternary structure, gene transcription will be inhibited.

Histone variants are proteins that substitute for the core canonical histones in nucleosomes in eukaryotes and often confer specific structural and functional features. The term might also include a set of linker histone (H1) variants, which lack a distinct canonical isoform. The differences between the core canonical histones and their variants can be summarized as follows: (1) canonical histones are replication-dependent and are expressed during the S-phase of cell cycle whereas histone variants are replication-independent and are expressed during the whole cell cycle; (2) in animals, the genes encoding canonical histones are typically clustered along the chromosome, are present in multiple copies and are among the most conserved proteins known, whereas histone variants are often single-copy genes and show high degree of variation among species; (3) canonical histone genes lack introns and use a stem loop structure at the 3’ end of their mRNA, whereas histone variant genes may have introns and their mRNA tail is usually polyadenylated. Complex multicellular organisms typically have a large number of histone variants providing a variety of different functions. Recent data are accumulating about the roles of diverse histone variants highlighting the functional links between variants and the delicate regulation of organism development.

H3K36me2 is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the di-methylation at the 36th lysine residue of the histone H3 protein.

References

↑ Alva, Vikram; Ammelburg, Moritz; Söding, Johannes; Lupas, Andrei N (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, James D.; Baker, Tania A.; Bell, Stephen P.; Gann, Alexander; Levine, Michael K.; Losick, Richard (2008). Molecular Biology of the Gene. Pearson/Benjamin Cummings. ISBN 978-0-8053-9592-1.^{[ page needed ]}
1 2 Arents, G; Moudrianakis, E N (21 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.
↑ Alva, Vikram; Ammelburg, Moritz; Söding, Johannes; Lupas, Andrei N (28 March 2007). "On the origin of the histone fold". BMC Structural Biology. 7: 17. doi: 10.1186/1472-6807-7-17 . PMC 1847821 . PMID 17391511.
↑ Baxevanis, Andreas D.; Landsman, David (1 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.
↑ Mariño-Ramírez, Leonardo; Kann, Maricel G; Shoemaker, Benjamin A; Landsman, David (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.

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[1] Alva, Vikram; Ammelburg, Moritz; Söding, Johannes; Lupas, Andrei N (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.

[2] Watson, James D.; Baker, Tania A.; Bell, Stephen P.; Gann, Alexander; Levine, Michael K.; Losick, Richard (2008). Molecular Biology of the Gene. Pearson/Benjamin Cummings. ISBN 978-0-8053-9592-1.^{[ page needed ]}

[pmid7479959-3] 1 2 Arents, G; Moudrianakis, E N (21 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.

[4] Alva, Vikram; Ammelburg, Moritz; Söding, Johannes; Lupas, Andrei N (28 March 2007). "On the origin of the histone fold". BMC Structural Biology. 7: 17. doi: 10.1186/1472-6807-7-17 . PMC 1847821 . PMID 17391511.

[5] Baxevanis, Andreas D.; Landsman, David (1 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.

[6] Mariño-Ramírez, Leonardo; Kann, Maricel G; Shoemaker, Benjamin A; Landsman, David (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.

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