Keratin 1 (K1) is a Type II intermediate filament (IFs) of the intracytoplasmatic cytoskeleton. It is co-expressed with and binds to Keratin 10, a Type I keratin, to form a coiled coil heterotypic keratin chain which then combine to constitute intermediate filaments. Keratin 1 and Keratin 10 are specifically expressed in the spinous and granular layers of the epidermis. Here, they are involved in both developing a physical barrier and various immune functions. Mutation of the protein causes forms of bullous congenital ichthyosiform erythroderma, and over expression is related to various cancers as it acts as a tumor-associated marker.
Structure
Keratin 1 is a type of fibrous protein of the keratin family and is primarily involved in the formation of rope-like intermediate filaments. More specifically, it is a Type II intermediate filament, meaning it is has a generally larger and neutral-basic structure compared to the small and acidic Type I counterparts. The rod-like structure of K1 consists of a coiled-coil central domain, which is surrounded by flexible, glycine-rich loops at the terminal ends. In all, K1 consists of 644 amino acids (aa) with the internal central domain consisting of four coiled segments made up of 313 amino acids, the 180 aa N-terminal head, and 151 aa C-terminal tail. These tail regions, rich in glycine loops, are known to assist in the assembly of mature intermediate filaments via head-to-tail attachment of K1 units. Additionally, low-complexity aromatic-rich kinked segments (LARKS), found at the tail ends, take on a β-sheet structure, which further assists in this head-to-tail linkage.
Type II cytokeratins, like K1, are clustered in a region of chromosome 12q13.13. Specifically, Keratin 1 is generated from the KRT1 gene. The protein has a molecular weight of roughly 66 kDa and an isoelectric point of roughly 8.3, further confirming that the protein is basic.
Function
The general formation of keratin intermediate filament is as follows: a type I keratin and a type II keratin bind to create a parallel heterodimer, which then uses a matching pair to create an antiparallel tetramer with two of each type. The tetramers go on to combine into a protofibril, which then combine with other protofibrils to make the final keratin intermediate filament. While its most common type I pair in the epidermis is K10, in the palms and soles of the feet, it can pair with Keratin 9 (K9). It is a protein layer consisting of keratins like K1, K10, and the proteins mentioned. The overall barrier of the epidermis is completed with the immune function of Langerhans cells. The importance to the skin barrier is seen in dysfunctional K1 cases, where the skin erodes and becomes blistered.
Beyond its role in providing structural toughness to the epidermis, K1 is also involved in the innate immune system of the epithelia that it is found in. It plays a role in local and systemic inflammation pathways and can even promote apoptosis in the smooth muscle of blood vessels affected with atherosclerosis. It acts as an inhibitor to the activation of the proinflammatory cytokine interleukin-18 (Il-18) in the case of an intact skin barrier. It works in tandem with Keratin 17 (K17), which induces inflammatory signaling pathways and protein synthesis in the case of a challenged skin barrier via injury, cancer, or irritants. Therefore, in a chronic or acute challenge to the skin barrier, K1 is down-regulated and K17 is up-regulated.
Last, K1 and its dimer partner, K10, are found in the sweat gland ducts of the skin. However, they are not present in any parts of a hair unit, like the follicle or the hair itself.
Interactions
Keratin 1 has been shown to interact with desmoplakin and PRKCE.
See also
- 34βE12