Prion proteins structure

Viles, J. H., Cohen, F. E., Prusiner, S. B., Goodin, D. B., Wright, P. E., and Dyson, H. J. (1999). Copper binding to the prion protein Structural implications of four identical cooperative binding sites. Proc. Natl. Acad. Sci. USA 96, 2042-2047. 

Walsh P, Simonetti K, Sharpe S (2009) Core structure of amyloid fibrils formed by residues 106-126 of the human prion protein. Structure 17 417 -26... 

Homshaw MP, McDermott JR, Candy JM, Lakey JH (1995) Copper binding to the N-terminal tandem repeat region of mammalian and avian prion protein structural studies using synthetic peptides. Biochem Biophys Res Commun 214 993-999... 

Q. Wang, A. Kretlow, M. Beekes, D. Naumann and L. Miller, In situ characterization of prion protein structure and metal accumulation in Scrapie-Infected Cells by Synchrotron Infrared and X-ray Imaging, Vib. Spectrosc., 2005, 38, 61-69. 

Re F, Sesana S, Barbiroli A, et al. Prion protein structure is affected by pH-dep)endent interaction with membranes a study in a model system. FEES Lett. 2008 582(2) 215-220. 

These results indicate that is it possible to change the fold of a protein by changing a restricted set of residues. They also confirm the validity of the rules for stability of helical folds that have been obtained by analysis of experimentally determined protein structures. One obvious impliction of this work is that it might be possible, by just changing a few residues in Janus, to design a mutant that flip-flops between a helical and p sheet structures. Such a polypeptide would be a very interesting model system for prions and other amyloid proteins. 

Wuthrich, K. and Riek, R. Tliree-dimensional structures of prion proteins. Adv. Protein Chem. 57 55-82,2001. 

Fig. 3. Structures of prion protein globular domains. (A) Crystal structure of the C-terminal domain dimer of Ure2p (pdb file 1HQO). (B) NMR structure of the C-terminal domain monomer of PrP (pdb file 1E1G).

A key feature of the protein-only hypothesis is that variants should represent distinct structural forms of the prion protein. A direct connection between filament structure and variants was made by Tanaka et al. (2004) using filaments made under different conditions (in this case, 4°C and 37°C). Filaments formed at 4°C were less stable against heating in 1.6% SDS and gave rise mostly to strong [PSI] variants after being transformed... 

Balguerie, A., Dos Reis, S., Ritter, C., Chaignepain, S., Coulary-Salin, B., Forge, V., Bathany, K., Lascu, I., Schmitter, J. M., Riek, R., and Saupe, S. J. (2003). Domain organization and structure-function relationship of the HET-s prion protein of Podospora anserina. EMBO J. 22, 2071-2081. 

Bousset, L., Belrhali, H., Janin,J., Melki, R., and Morera, S. (2001a). Structure of the globular region of the prion protein Ure2 from the yeast Saccharomyces cerevisiae. Structure 9, 39-46. 

Gasset, M., Baldwin, M. A., Fletterick, R.J., and Prusiner, S. B. (1993). Perturbation of the secondary structure of the scrapie prion protein under conditions that alter infec-... 

Lopez Garcia, F., Zahn, R., Riek, R., and Wiithrich, K. (2000). NMR structure of the bovine prion protein. Proc. Natl. Acad. Sci. USA 97, 8334-8339. 

Umland, T. C., Taylor, K. L., Rhee, S., Wickner, R. B., and Davies, D. R. (2001). The crystal structure of the nitrogen regulation fragment of the yeast prion protein Ure2p. Proc. Natl. Acad. Sci. USA 98, 1459-1464. 

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. 

---