Keratins structural models

TABLE lO-III Principal Developments in a-Keratin Structural Models... 

Alpha farnesene, structure of, 207 Alpha helix (protein), 1038 Alpha-keratin, molecular model of, 1039... 

Parry, D. A. D. (1995). Hard u-keratin IF A structural model lacking a head-lo-lail molecular overlap but having hybrid features characteristic of both epidermal keratin and vimentin IF. Proteins 22, 267-272. 

Norlen, L. and Al-Amoudi, A., Stratum corneum keratin structure, function, and formation the cubic rod-packing and membrane templating model, J. Invest. Dermatol., 123, 715, 2004. 

An important feature of the diffraction pattern predicted by these models is the occurrence of a series of meridional reflections which are orders of a 10.33 A periodicity. This periodicity is associated with the axial projection of the asymmetric unit, which consists of seven residues. Astbury and Bell (1939) had noted such a periodicity in a-keratin and given spacings for the first four orders, whereas a spacing of 1.49 A, close to the seventh order, had been noted by MacArthur (1943). More recently, meridional scatter in the vicinity of the fifth, ninth, and eleventh orders has been reported (Fraser and MacRae, 1961b). In a field where structural models had been considered plausible if they predicted one reflection the suggestion of the coiled-coil models was thus a very significant advance. 

The jS form of keratin requires still additional models. And, continuing the order of decreasing certainty, these models are again less well corroborated by experimental observations than are the a-helix or a-keratin structures. Pauling and Corey (1598) presented the pleated sheets to explain /3-keratins. These sheets are made up of extended peptide chains H bonded essentially side by side. Two are shown in Fig. 10-7. 

Recently, the nomenclature in the field of fibrous keratin structure has been changed to take into account new knowledge developed over the last few years by various groups of protein chemists, cell biologists, and molecular biologists. Crewther and Fraser and their co-workers (6,7) developed models of molecular organization that can accommodate... 

In another approach, Parnigotto and coworkers reconstructed corneal structures in vitro by using corneal stroma containing keratocytes to which corneal epithelial cells from bovine primary cultures were overlaid [73], However, this particular corneal model did not contain an endothelial layer. This model was histochemically characterized and the toxicity of different surfactants was tested using MTT methods. This stroma-epithelium model has been reported to show a cornea-like morphology, where a multilayered epithelial barrier composed of basal cells (of a cuboidal shape) and superficial cells (of a flattened shape) is noted. Furthermore, the formation of a basement membrane equivalent and expression of the 64-kDa keratin were reported, indicating the presence of differentiated epithelial cells. The toxicity data for various surfactants obtained with this model correlate well with those seen by the Draize test [73], However, this corneal equivalent was not further validated or used as a model for permeation studies. 

Figure 7-31 A model for the structure of keratin microfibrils of intermediate filaments. (A) A coiled-coil dimer, 45-nm in length. The helical segments of the rod domains are interrupted by three linker regions. The conformations of the head and tail domains are unknown but are thought to be flexible. (B) Probable organization of a protofilament, involving staggered antiparallel rows of dimers. From Jeffrey A. Cohlberg297...

The Structure of the a-Keratins Was Determined with the Help of Molecular Models The fi-Keratins Form Sheetlike Structures with Extended Polypeptide Chains Collagen Forms a Unique Triple-Stranded Structure Globular Protein Structures Are Extremely Varied and Require a More Sophisticated Form of Analysis Folding of Globular Proteins Reveals a Hierarchy of Structural Organization... 

The Structure of the a-Keratins Was Determined with the Help of Molecular Models... 

In almost all instances of biological mineralization fibrous proteins represent the bulk of the organic matrix. In the past, this phenomenon has been interpreted to mean that proteins such as collagen, keratin or elastin are the key elements in mineralization by providing nucleation sites and at the same time offering structure and space for oriented crystal growth. However, with the advance in the field of biomineralization this model came under severe attack. At present, there is no universal concept which could explain all the intriguing facets of phosphate deposition in cellular systems. 

Fig. 5. Predicted conformation of the pentapeptide repeat C-X-Y-Z-C in trichocyte keratin-associated proteins. Glutamine and arginine residues are found commonly in the X position, prolines in the Yposition, and serines and threonines in the Z position. The structure is based on the known conformation of a similar repeat in snake neurotoxin. The model shows a disulphide bond-stabilized /5-bend with a potential hydrogen bond (dotted). A string of these /5-bends, linked by bonds about which there is relatively free rotation, has been proposed as a model for this important family of matrix proteins in trichocyte keratin (Fraser et al, 1988). Figure from Fraser et al (1988) with permission from Elsevier.

Abstract The utility of confocal Raman microscopy to study biological events in skin is demonstrated with three examples, (i) monitoring the spatial and structural differences between native and cultured skin, (ii) tracking the permeation and biochemical transformation in skin of a Vitamin E derivative and (iii) tracking the spatial distribution of three major skin proteins (keratin, collagen, and elastin) during wound healing in an explant skin model. 

In 1975, Michaels et al.33 presented a conceptual model of the arrangement of corneocytes and lipids in stratum corneum. They envisaged stratum corneum as a brick and mortar structure with the keratin filled corneocytes as bricks and the intercellular lipids as mortar. This model was further explored by Elias and co-worker.34-37 This model does not per se include a structure-function perspective on the barrier but has had a tremendous impact on the research on stratum corneum and its composition, function, and the regulation of homeostasis. 

In 1994 Forslind presented a more structure-function orientated model, the domain mosaic model.38 With the background given previously, the requirements on the stratum corneum barrier can be summarized as follows the barrier should be watertight but still allow a small, controlled amount of water to leak from the system in order to keep the corneocyte keratin hydrated. 

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