Amyloid prion protein

Other IRRAS applications to peptides and proteins. In addition to the pulmonary surfactant system, a variety of other applications employing IRRAS to study peptide and protein conformation and orientation have appeared. The secondary structure conversion of the amyloid (prion)-protein in the normal form into the abnormal form is the main cause of several human and animal diseases, such as Alzheimer s disease [68]. The secondary structure of the first 40 residues of the amyloid protein was detected by circular dichroism (CD) in aqueous solution and with IRRAS at the interface. A stable /1-sheet-enriched state of the amyloid is formed at the air-water interface, in contrast to the initial bulk solution containing high a-helix/random coil and low /l-sheet parts. The change in the pH going from bulk (alkaline pH) to the interface (neutral or slightly acidic pH) can have effects on the conformation at the interface. Another alternative might be the intrinsic hydrophobicity of the air-water interface, which is a hydrophobic-hydrophilic system with air as the hydrophobic part. 

Safar J, Roller PP, Gajdusek DC et al (1993) Thermal stability and conformational transitions of scrapie amyloid (prion) protein correlate with infectivity. Protein Sci 2 2206-2216... 

Figure 4 (A) Solvent-induced conformational transition of PrP27-30 scrapie amyloid (prion) protein in the solid state on quartz glass. Films were exposed for 20 to 30 min to SDS, sodium dodecyl sulfate, TFE, trifluorethanol HFIP, hexafluorisopropanol TFA, trifluoro-acetlc acid FA, 99% formic acid, f is the spectrum with no treatment at 23°C. (B) Data on PrP27-30 obtained under various conditions, deconvoluted into five basis curves using the convex-constraint algorithm. (—)/S-tum type I or III and/or 3,o-type helix (.) alpha...

The conformational plasticity supported by mobile regions within native proteins, partially denatured protein states such as molten globules, and natively unfolded proteins underlies many of the conformational (protein misfolding) diseases (Carrell and Lomas, 1997 Dobson et al., 2001). Many of these diseases involve amyloid fibril formation, as in amyloidosis from mutant human lysozymes, neurodegenerative diseases such as Parkinson s and Alzheimer s due to the hbrillogenic propensities of a -synuclein and tau, and the prion encephalopathies such as scrapie, BSE, and new variant Creutzfeldt-Jacob disease (CJD) where amyloid fibril formation is triggered by exposure to the amyloid form of the prion protein. In addition, aggregation of serine protease inhibitors such as a j-antitrypsin is responsible for diseases such as emphysema and cirrhosis. 

Volume 309. Amyloid, Prions, and Other Protein Aggregates Edited by Ronald Wetzel... 

Baskakov, I. V., and Bocharova, O. V. (2005). In vitro conversion of mammalian prion protein into amyloid fibrils displays unusual features. Biochemistry 44, 2339-2348. 

Chan,J. C., Oyler, N. A., Yau, W. M., and Tycko, R. (2005). Parallel beta-sheets and polar zippers in amyloid fibrils formed by residues 10-39 of the yeast prion protein Ure2p. Biochemistry 44, 10669-10680. 

In this section, we discuss several recent proposals for how the proteins are arranged in amyloid filaments of fungal prion proteins in light of current experimental data. 

Balguerie, A., Dos Reis, S., Coulary-Salin, B., Chaignepain, S., Sabourin, M., Schmitter, J. M., and Saupe, S.J. (2004). The sequences appended to the amyloid core region of the HET-s prion protein determine higher-order aggregate organization in vivo. J. Cell Sci. 117, 2599-2610. 

Amyloid aggregates of the HET-s prion protein are infectious. Proc. Natl. Acad. Sci. USA 99, 7402-7407. 

DeMarco, M. L., and Daggett, V. (2004). From conversion to aggregation Protofibril formation of the prion protein. Proc. Natl. Acad. Sci. USA 101, 2293-2298. Diaz-Avalos, R., Long, C., Fontano, E., Balbirnie, M., Grothe, R., Eisenberg, D., and Caspar, D. L. D. (2003). Cross-beta structure of an amyloid-forming peptide studied by electron nano-crystallography. Fibre Diffract. Rev. 11, 79-86. 

Diaz-Avalos, R., King, C. Y., Wall,J., Simon, M., and Caspar, D. L. (2005). Strain-specific morphologies of yeast prion amyloid fibrils. Proc. Natl. Acad. Sci. USA 102,10165-10170. Donne, D. G., Viles, J. H., Groth, D., Mehlhom, I., James, T. L., Cohen, F. E., Prusiner, S. B., Wright, P. E., and Dyson, H.J. (1997). Structure of the recombinant full-length hamster prion protein PrP(29-231) The N terminus is highly flexible. Proc. Natl. Acad. Sci. USA 94, 13452-13457. 

Hope, J., Shearman, M. S., Baxter, H. C., Chong, A., Kelly, S. M., and Price, N. C. (1996). Cytotoxicity of prion protein peptide (PrP106-126) differs in mechanism from the cytotoxic activity of the Alzheimer s disease amyloid peptide, A [S 25-35. Neurodegeneration 5, 1-11. 

Inouye, H., and Kirschner, D. A. (1996). Refined fibril structures The hydrophobic core in Alzheimer s amyloid /1-protein and prion as revealed by X-ray diffraction. Ciba Found. Symp. 199, 22-35 discussion 35-9. 

Wille, H., Baldwin, M. A., Cohen, F. E., DeArmond, S. J., and Prusiner, S. B. (1996). Prion protein amyloid Separation of scrapie infectivity from PrP polymers. Ciba Found. Symp. 199, 181-199 discussion 199-201. 

Fibrous Proteins Amyloids. Prions and Beta Proteins... 

Prion diseases have attracted immense attention over the past decade, prompted, in part, by the outbreak of mad cow disease in the United Kingdom. The most common prion disease is sporadic Creutzfeldt-Jakob disease (CJD). Clinically, CJD is characterized by a rapidly progressive dementia accompanied variably by early-onset seizures, insomnia, disordered movements, and psychiatric disturbances the disease is uniformly fatal. Histochemically, the principal pathological feature of prion disease is the abnormal accumulation of an amyloid-like material composed of prion protein (PrP), which is encoded by a single gene on the short arm of chromosome 20. 

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