RESUMEN
The prion protein PrP(C) in transmissible spongiform encephalopathy converts to the pathogenic isoform PrP(Sc) containing less alpha-helical structure and a greater beta-pleated sheet content. The stability of PrP(C) protein is partly dependent on the disulphide bond between two alpha-helices designated B and C. Further stability could arise from ligand complexes of Cu(II) ions formed with carboxylic acid side chains in PrP(C). Electron spin resonance (E.S.R.) spectra and atomic absorption measurements have shown for alpha-keratin that the formation of ligands by Cu(II) is 10(2) more rapid than interaction of Cu(II) with ionised thiols X-S(-) which form X-S-Cu(+). X-S(-) destabilises disulphide bonds by thiol-disulphide interchange. When insufficient Cu(II) is present to form ligands with all available sites in PrP(C) then unblocked X-S(-) groups could potentially destabilise the disulphide bonds by thiol-disulphide interchange followed by reformation of the disulphide bond in the beta form of PrP(Sc) and the release of X-S(-) to interact with other PrP(C).
Asunto(s)
Cobre/farmacología , Cistina/efectos de los fármacos , Proteínas PrPC/efectos de los fármacos , Proteínas PrPSc/química , Compuestos de Sulfhidrilo/farmacología , Animales , Cobre/deficiencia , Cistina/química , Espectroscopía de Resonancia por Spin del Electrón , Humanos , Ligandos , Modelos Moleculares , Proteínas PrPC/química , Conformación Proteica/efectos de los fármacos , Estructura Secundaria de Proteína/efectos de los fármacos , Espectrofotometría AtómicaRESUMEN
Recent Fourier transform infrared spectroscopy (FTIR) with attenuated total reflection technique (ATR) has been applied to alpha-keratin fibers (horse-hair) extended in water both at 21 and 95 degrees C. Infrared absorption bands in the Amide 1 region indicated that at extensions to 40-50% strain in water at 21 degrees C alpha-helices had completely disappeared and parallel beta-sheets were formed [Appl. Spectrosc. 55 (2001) 552]. However, when the hair fibers were extended to the same strain at 95 degrees C in water the result was the formation of anti-parallel beta-sheets. These results suggest that the relatively more stable anti-parallel beta-state [Polymer 10 (1969) 810] is only attained in extended alpha-keratin fibers at elevated temperatures and must result from major molecular rearrangement. It was concluded that the alpha-helices in the intermediate filaments (IFs) of alpha-keratin fibers must be parallel. This is in contrast to the previously accepted orientation of anti-parallel alpha-helices, based primarily on findings of X-ray diffraction studies of the structure of beta-keratin in highly extended fibers [Polymer 10 (1969) 810; Keratins, IL: Thomas Springfield (1972); Nature 316 (1985) 767].
Asunto(s)
Queratinas/química , Animales , Caballos , Filamentos Intermedios , Estructura Secundaria de Proteína , Espectroscopía Infrarroja por Transformada de Fourier/métodosRESUMEN
Goniophotometry has enabled measurement of the angle that the surface of the cuticle (the scales) of a human hair fiber makes with the axis of the hair shaft. This measuring technique has been used to obtain the change of this scale angle with extension of a hair fiber under fixed conditions of temperature and relative humidity. Based on a simple model of overlapping scales of the hair cuticle, analysis shows that, for hair fibers extended to strains above 10% at 35% relative humidity and at 35 degrees C, overlapping scales become progressively detached from each other. This scale detachment has been suggested to result from the mechanical failure of the endocuticle layer in the scale structure. This endocuticle layer is low in disulfide cross-linking, which would result in a lowered stiffness and greater extensibility, as indicated by the higher swelling of the layer in water as against the highly cross-linked exocuticle layers. The greater extensibility of the endocuticle would also explain the greater distortion of this layer under stress, but it would not follow that endocuticular failure under stress should result. An alternative mechanism of failure of adhesion between overlapping scales in the cuticle is suggested, based on the involvement of the hydrophobic upper-beta-layer with its surface of 18-methyleicosanoic acid (18-MEA), which may provide mobility and a reduction in adhesion between scales. This potential failure of the cementing of the overlapping scale structure due to the 18-MEA is discussed, with particular reference to the standard permanent setting procedure of human hair.