The human skin consists of two layers: an outermost layer called the epidermis and a layer underneath called the dermis. In individuals with healthy skin, there are protein anchors between these two layers that prevent them from moving independently from one another (shearing). In people born with EB, the two skin layers lack the protein anchors that hold them together, resulting in extremely fragile skin—even minor mechanical friction (like rubbing or pressure) or trauma will separate the layers of the skin and form blisters and painful sores. Sufferers of EB have compared the sores with third-degree burns. Furthermore, as a complication of the chronic skin damage, people suffering from EB have an increased risk of malignancies (cancers) of the skin.
A 2014 study classified cases into three types—epidermolysis bullosa simplex (EBS), junctional epidermolysis bullosa (JEB), and dystrophic epidermolysis bullosa (DEB) — and reviewed their times of death. The first two types tended to die in infancy and the last in early adulthood. In a survey of 11 families affected by the disease, lack of awareness of the disease by both the public and health care providers raised concerns about the care provided as well as insensitive comments by adults and bullying by children.
Recent research has focused on changing the mixture of keratins produced in the skin. There are 54 known keratin genes—of which 28 belong to the type I intermediate filament genes and 26 to type II—which work as heterodimers. Many of these genes share substantial structural and functional similarity, but they are specialized to cell type and/or conditions under which they are normally produced. If the balance of production could be shifted away from the mutated, dysfunctional keratin gene toward an intact keratin gene, symptoms could be reduced. For example, sulforaphane, a compound found in broccoli, was found to reduce blistering in a mouse model to the point where affected pups could not be identified visually, when injected into pregnant mice (5 µmol/day = 0.9 mg) and applied topically to newborns (1 µmol/day = 0.2 mg in jojoba oil).
Protein dimers are either homodimers (complexation of identical monomers) or heterodimers (complexation of non-identical monomers). These dimers are common in catalysis and regulation. However, the molecular principles of protein dimer interactions are difficult to understand mainly due to the geometrical and chemical characteristics of proteins. Nonetheless, the principles of protein dimer interactions are often studied using a dataset of 3D structural complexes determined by X-ray crystallography. A number of physical and chemical properties govern protein dimer interactions. Yet, a handful of such properties are known to dominate protein dimer interfaces. Here, we discuss the differences between homodimer and heterodimer interfaces using a selected set of interface properties.
Protein subunit interaction (either homodimer or heterodimer) is an important phenomenon in regulation and catalysis. Thousands of such interactions are theoretically possible in a combinatorial manner. The task of documenting each of these interactions is laborious. Therefore, prediction of subunit interaction sites either from folded structures or from primary sequences is required. However, this objective is currently ambitious due to the limited knowledge on the principles of protein subunit interactions using structural data. Therefore, it is our interest to study the nature of subunit interactions. Several studies report on these interactions. Jones & Thornton (used 59 protein complexes) , Xu & colleagues (used 319 protein-protein interfaces) , Tsai & colleagues (used 362 protein-protein interfaces) , Lo Conte & colleagues (used 75 hetero-complexes) [ 4 ], Chakrabart & Janin (used 70 hetero-complexes) , Brinda & colleagues (used 20 homodimers) , Bahadur and colleagues (used 122 homodimers) , Nooren and Thornton (used 39 protein dimers) , Caffrey and colleagues (used 64 protein-protein interfaces)  and Zhanhua and colleagues (used 65 heterodimers) , utilized a dataset of protein complexes determined by X-ray crystallography to examine the properties of subunit interaction. Protein subunit interfaces in these studies have been characterized using geometrical properties (interface size, planarity, sphericity and complementarity) and chemical properties (the types of amino acid chemical groups, hydrophobicity, electrostatic interactions and H-bonds). These studies are influenced by dataset size and their characteristics. However, the analyses are based on limited datasets consisting of heterogeneous (disproportionate mixture of homodimers and heterodimers) data.
The analyses report on the role of inter-subunit H-bonds in protein subunit association. The numbers of H-bonds vary in different studies. [2–4– 7–8–11] On average, Bahadur & colleagues show 9.0 H-bonds per homodimer interface with an r value of 0.75 (Pearson correlation coefficient) between H-bonds and interface area.  Jones & Thornton (used 32 homodimers) show 0.88 H-bonds per 100 Å2 interface area with an r value of 0.77 between H-bonds and interface area.  Lo Conte et al. show an average of 10.1 H-bonds with one H-bond per 170 Å2 interface area and an r value of 0.84 between H-bonds and interface area. [ 4] Xu & colleagues also show 11 H-bonds per subunit with an r value of 0.89 between H-bonds and interface area.  The r value between H-bonds and interface area in these studies varies from 0.75 to 0.89. This variation is influenced primarily by dataset size and nature of data.
Previous studies also show that hydrophobic effect plays an important role in protein association [3–7–12 ], yet not as much as in protein folding.  There studies showed that protein interfaces are more hydrophobic than surfaces, but less than interior. Hydrophobic effect was measured by the buried non-polar surface area (or percent burial) of residue types.  The study showed that the ratio between buried hydrophobic and buried hydrophilic residues is approximately 1.5.  Hydrophobic residues (except ALA) and the charged residue ARG are predominantly present at protein-protein interfaces with TYR and TRP having highest propensity. [4 –6–7–12–13]
Interface size is yet another important property widely used to describe protein-protein interfaces and it is usually characterized by interface area. The number of interface residues is linearly correlated to interface area (r ≥ 0.96) in several studies. [5 –7] However, the mean number of interface residues varies between these studies. It is shown that the mean is 52 , 57 , 53.7 , 44.4 (for homodimers) and 42.2 (for heterodimers).  Thus, the number of interface residues vary within a narrow range of 42 and 57 in these studies.
Here, we created two extended datasets of mutually exclusive homodimers and heterodimers. We believe that these exclusive datasets can reduce data bias to differentiate heterodimer and homodimer interfaces.
Not enough information for processing, but gene information is important to make sure that gene editing may be a cure for this problem.
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