Prion definition

The search for life in the cosmos requires a generalised, universal definition of life. This must take into account the properties of systems ranging from viruses, prions, denucleated cells or endospores to life in a test tube, computer viruses or even to robots which are capable of self-replication. 

To meet the infectivity requirement in the definition of a prion, the abnormal form of the protein must be transmissible to other cells and organisms of the same species. In yeast and filamentous fungi, infectious agents such as viruses and plasmids are naturally transmitted by cytoplasmic mixing during mating or heterokaryon formation (Wickner, 2001). 

The sizes of the prion domains vary from 70 amino acid residues (HET-s) to 250 amino acid residues (Rnqlp) (Fig. 1), but their borders are not precisely defined by functional criteria since these domains may be subjected to sizeable truncations while retaining their prionogenic properties (Edskes and Wickner, 2002 Ross et al., 2005). Nor are they precisely defined by the extent of N/Q-rich tracts since not all prion domains have them and the preponderance of these residues can vary within a given prion domain. Since the functional domains tend to have globular folds (Section II.B), an operational definition of a prion domain may be that it terminates with the last (or first) residue that is not part of the functional domain, although this definition is applicable only when that fold is known. 

Although definitive structural solutions for any of the prion domain filaments have yet to be achieved, the body of experimental data is growing and it is possible that the fold and packing of prion domains in HET-s filaments differ qualitatively from those in Ure2p or Sup35p filaments (Section VI). 

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. 

SRM which include CNS tissue are tissues from animals that are known to carry, transfer, or perpetuate infectivity of the BSE causative agent, prions. Because BSE is an adult-onset disease, identification of tissues as SRM is dependent on the age of the animal at slaughter, and definitions of SRM vary by country, based on differences in interpretation of scientific evidence and the amount of risk allowed (Table 1). Care must be taken when removing SRM (including CNS tissue) to prevent contamination of products due to improper or incomplete removal of SRM and to prevent cross-contamination of SRM to meat products via personnel or equipment. 

We use the word prion to mean an infectious protein, a protein that is altered in some way so that it does not carry out its normal function properly, but has acquired the ability to convert the normal form of the protein to the same abnormal (nonfunctional) form. By this definition, three properties are expected of a prion that are in contrast to the corresponding properties of a nucleic acid replicon (Wickner, 1994). 

In biology, the trouble with definitions is far worse than in mathematics. Few biologists ever use the word proof — it is far too exact. Doctors rarely use the word cure. Who knows, after all Remission is a more comfortable word, if only because it means very little "the illness seems to have gone away for now, for all I can see I have no idea if it will come back". Nature deftly sidesteps our clumsy swings at a definition. How does one define life Reproduction and some form of metabolism seem to be musts, but then is a virus alive It has no metabolism of its own and so falls outside most definitions of life. If you can define life to encompass a virus, then how about the infectious prion, which is simply a protein ... 

Biology can be a very complex science, and its principles are not always easy to define. Defining life itself is not easy, either, and there has been no totally satisfactory definition of life. As more and more is known about subcellular structures that prey on living things (e.g., prions and viruses), it is clear that the demarcation between living and nonliving things is not well defined. 

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