Prion protein diversity

PRION PROTEIN DIVERSITY AND DISEASE IN THE TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES... 

HPLC was used by Lu and Chang (2001) to identify conformational isomers of mPrP(23-231). The data produced from the study indicated that the reduced form of mouse prion protein was able to exist as at least four diverse isoforms and were able to be separated by HPLC. More importantly, this technique faciliated the isolation of the isomers and confirmation of the protein molecule. 

Lee S, Antony L, Hartmann R et al (2010) Conformational diversity in prion protein variants influences intermolecular beta-sheet formation. EMBO J 29 251-262... 

Chen W, Van der Kamp MW, Daggett V (2010) Diverse effects on the native /(-sheet of the human prion protein due to disease-associated mutations. Biochemistry 49 9874... 

Endo T, Groth D, Prusiner SB, Kobata A (1989) Diversity of oligosaccharide structures linked to asparagines of the scrapie prion protein. Biochemistry 28 8380... 

The combined term prion protein (PrP) refers to tbe protein ratber than tbe infectious agent. However, it is increasingly apparent tbat PrP exists in a wide variety of forms tbat are normal (e.g., PrP -), TSE-associated (e.g., PrP , PrPflJ, PrP ), neither (e.g., various recombinant and/or mutated versions of tbe PrP structure), or both. This structural diversity complicates the use of Prusiner s original terms PrP " (cellular PrP) and PrP (scrapie PrP). These terms are still useful under many circumstances, but often need further, more operational and/or functional qualification as the sophistication of current studies increases. Eor instance, since protease resistance is most commonly used to discriminate normal and TSE-associated forms of PrP, the operational terms PrP-sen (protease-sensitive PrP) and PrP-res (protease-... 

This chapter has reviewed the application of ROA to studies of unfolded proteins, an area of much current interest central to fundamental protein science and also to practical problems in areas as diverse as medicine and food science. Because the many discrete structure-sensitive bands present in protein ROA spectra, the technique provides a fresh perspective on the structure and behavior of unfolded proteins, and of unfolded sequences in proteins such as A-gliadin and prions which contain distinct structured and unstructured domains. It also provides new insight into the complexity of order in molten globule and reduced protein states, and of the more mobile sequences in fully folded proteins such as /1-lactoglobulin. With the promise of commercial ROA instruments becoming available in the near future, ROA should find many applications in protein science. Since many gene sequences code for natively unfolded proteins in addition to those coding for proteins with well-defined tertiary folds, both of which are equally accessible to ROA studies, ROA should find wide application in structural proteomics. 

Observation of living systems shows them to be complex mixtures of different chemicals each of which functions to support one or more of the necessary tasks required to keep the organism alive . At one end of the spectrum of complexity lie the viruses and related simple proteins, such as prions, which cannot replicate by themselves but reproduce with the aid of other, higher, life forms. They therefore fulfill the definition of life to a very limited extent. At the other end of the spectrum there are the multicellular organisms such as humans with a vast diversity of processes that relate directly, and often more subtly, to the basic requirements of life. Even here, though, there is often a dependence on another living system. For example, humans cannot survive without vitamin Bi2 but are unable to synthesize it and must rely on external agents for its production. 

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