N-terminal tail domain

The histone variants of H2A form the largest family of identified histone variants (Redon et al, 2002 Sarma and Reinberg, 2005). This could be associated with both the strategic position that has the histone H2A within the histone octamer and the less stable interaction of the H2A-H2B dimmer with both DNA and the (H3-H4)2 tetramer within the nucleosome (Luger et al, 1997). Most of the histone H2A variants exhibit a unique property in addition to the N-terminal tail domain, they also posses an unstructured C-terminal tail. To date four variants of histone H2A have been discovered. These include, H2AZ, H2A.X, macroH2A and H2A.Bbd. The highest differences in the primary structure of these H2A variants are observed in their C-terminal portion. Each of these variants could be efficiently incorporated in the nucleosome in vitro and in vivo. The presence of these variants alter the structural and functional properties of the nucleosome distinctly. 

Although the histone fold was first described from the structure of the histone octamer core of the nucleosome [17], the high a-helical content was predicted much earlier [43]. The core histones possess three functional domains (1) the histone fold domain, (2) an N-terminal tail domain, and (3) various accessory helices and less structured regions. The N-terminal tail domains of the core histones are currently the focus of intense research. Covalent modifications of residues in these unstructured domains appear to modify local chromatin structure, either directly or... 

Histone methylation was first reported in 1964 [118], Core histones H2B, H3, and H4 are modified by methylation (Fig. 1). H3 and H4 are modified at lysines and arginines located primarily in the N-terminal tail. Histone methylation does change the charge of the protein at physiological pH. However, methylation does increase the hydrophobicity of the lysine residue and reduces its ability to form hydrogen bonds [119]. The sites of methylation (Lys-20 in H4 and Lys-27 in H3) are positioned at the boundary between the very basic N-terminal tail domain and the more hydrophobic sequence of the remainder of the molecule. Lys-20 of histone H4 is also in the basic region that binds to nucleosomal DNA [120]. Methylation at these sites may alter nucleosome structure [121,122]. 

Fig. 1. Histone modifications on the nucleosome core particle. The nucleosome core particle showing 6 of the 8 core histone N-terminal tail domains and 2 C-terminal tails. Sites of post-translational modification are indicated by coloured symbols that are defined in the key (lower left) acK = acetyl lysine, meR = methyl arginine, mcK = methyl lysine, PS = phosphoryl serine, and uK = ubiquitinated lysine. Residue numbers are shown for each modification. Note that H3 lysine 9 can be either acetylated or methylated. The C-terminal tail domains of one H2A molecule and one H2B molecule are shown (dashed lines) with sites of ubiquitination at H2A lysine 119 (most common in mammals) and H2B lysine 123 (most common in yeast). Modifications are shown on only one of the two copies of histones H3 and H4 and only one tail is shown for H2A and H2B. Sites marked by green arrows are susceptible to cutting by trypsin in intact nucleosomes. Note that the cartoon is a compendium of data from various organisms, some of which may lack particular modifications e.g., there is no H3meK9 in S. cerevisiae. (From Ref [7].)...

C-termini and a large glycosylated extracellular loop between transmembrane domains 3 and 4. The proteins show the most homology in their transmembrane spanning domains, particularly domains 1, 2, and 4-8, which may be involved in moving the transmitter across the membrane. The transporters are substrates for PKC-dependent phosphorylation, which reduces their activity. The dopamine transporter is phosphorylated on the extreme end of the N-terminal tail, and consensus phosphorylation sites for various other kinases are present in the intracellular loops and domains [20-22] (Fig. 12-4). The dopamine and norepinephrine transporters form functional homo-oligomers, although it is not known if this is required for transport activity, and the transporters also interact with many other membrane proteins that may control their cell-surface expression or other properties. 

It is noteworthy that Src-induced increase in NR1-NR2A receptor activity is promoted by the coexpression of postsynaptic density protein known as PSD-95 [37]. PSD-95 is a scaffolding protein consisting of multiple protein-protein interaction domains - three N-terminal PDZ domains, an SH3 domain and a C-terminal guanyl-ate kinase domain. The first two PDZ domains interact with the NR2 C-terminal tails while the third PDZ domain... 

Fig. 70. Domains 2 (cylinders) and N-terminal tails of B- and C-type subunits around the quasi-6-fold axis in tomato bushy stunt virus. The association of the three C-subunit tails around the quasi-6-fold forms domain 1 (see Fig. 84).

NMR characterization of the recombinant mouse,hamster, bovine and human prion proteins showed that all these molecules share a common architecture, consisting of a flexible unstructured N-terminal tail of about 100 residues from position 23 to position 124 attached to a globular domain within residues 125-228. The globular domain contains a double-stranded anti-parallel /1-sheet and three ot-helices (Fig. 6). 

DNA sequence-dependent nucleosome structural and dynamic polymorphism. A role for H2B N-terminal tail proximal domain... 

Sivolob, A., Lavelle, C., and Prunell, A. (2003) Sequence-dependent nucleosome structural and dynamic polymorphism. Potential involvement of histone H2B N-terminal tail proximal domain. J. Mol. Biol. 326, 49-63. 

Zig-zag fiber morphology persists at later stages of digestion and is attributed to retention of the globular domain of LH in fiber The three-dimensional organization of nucleosomes in extended (low ionic strength) chromatin fibers requires the globular domain of LHs and either the tails of LH or the N-terminal tails of H3... 

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