T1 - The controversial protein-only hypothesis of prion propagation

The Virion Hypothesis states that TSEs are caused by a replicable informational molecule (which is likely to be a nucleic acid) bound to PrP. Many TSEs, including Scrapie and BSE, show strains with specific and distinct biological properties, a feature which supporters of the Virion hypothesis feel is not explained by prions. The presence of a nucleic acid bound to the protein would explain the strains observed. It has also been shown that TSEs including BSE retain their host-specific properties after passage through many different species. [42]

Evidence in favor of a protein-only hypothesis include:[39]

Evidence in favor of a viral hypothesis include:[39]

Beyond the protein-only hypothesis: A ..

The concept of signal‐mediated targeting of proteins was expanded into a generalised hypothesis of protein topogenesis by Günter Blobel in 1980.

protein only hypothesis translation in English-French dictionary

A breakthrough occurred when researchers discovered that the infectious agent consisted mainly of a specific protein, which Prusiner called PrP (an abbreviation for "prion protein"). This protein is found in the of normal (its precise function is not known), but an altered shape distinguished the infectious agent. The normal one is called PrPC, while the infectious one is called PrPSC (the 'C' refers to 'cellular' PrP, while the 'SC' refers to '', a prion disease occurring in sheep). It is hypothesized that the distorted protein somehow induces normal to also become distorted, producing a that both propagates the disease and generates new infectious material. Since the original hypothesis was proposed, a for the PrP protein has been isolated (the PRNP gene), several that cause the variant shape have been identified and successfully cloned, and studies using genetically altered mice have bolstered the prion hypothesis. In 2004, researchers succeeded in infecting mice with artifical prions composed entirely of synthetic PrPSC protein, confirming the "protein only" model for prion disease.

KW - Protein-only hypothesis
Wickner W (1979) The assembly of proteins into biological membranes: the membrane trigger hypothesis. Annual Review of Biochemistry 48: 23–45.

What was the proteins first hypothesis? | Yahoo Answers

AB - Prions are self-propagating proteinaceous infectious agents capable of transmitting disease in the absence of nucleic acids. The nature of the infectious agent in prion diseases has been at the center of passionate debate for the past 30 years. However, recent reports on the in vitro generation of prions have settled all doubts that the misfolded prion protein (PrP Sc) is the key component in propagating infectivity. However, we still do not understand completely the mechanism of prion replication and whether or not other cellular factors besides PrPSc are required for infectivity. In this article, we discuss these recent reports under the context of the protein-only hypothesis and their implications.

Matlin KS (2011) Spatial expression of the genome: the signal hypothesis at forty. Nature Reviews Molecular Cell Biology 12: 333–340.

History of the Signal Hypothesis

After a hypothesis has been formed, scientists conduct experiments to test its validity. are systematic observations or measurements, preferably made under conditions—that is, under conditions in which a single variable changes. For example, in our extinction scenario, iridium concentrations were measured worldwide and compared. A properly designed and executed experiment enables a scientist to determine whether the original hypothesis is valid. Experiments often demonstrate that the hypothesis is incorrect or that it must be modified. More experimental data are then collected and analyzed, at which point a scientist may begin to think that the results are sufficiently reproducible (i.e., dependable) to merit being summarized in a , a verbal or mathematical description of a phenomenon that allows for general predictions. A law simply says happens; it does not address the question of . One example of a law, the , which was discovered by the French scientist Joseph Proust (1754–1826), states that a chemical substance always contains the same proportions of elements by mass. Thus sodium chloride (table salt) always contains the same proportion by mass of sodium to chlorine, in this case 39.34% sodium and 60.66% chlorine by mass, and sucrose (table sugar) is always 42.11% carbon, 6.48% hydrogen, and 51.41% oxygen by mass. (For a review of common units of measurement, see Essential Skills 1 in .) The law of definite proportions should seem obvious—we would expect the composition of sodium chloride to be consistent—but the head of the US Patent Office did not accept it as a fact until the early 20th century.

Du, Z & Li, L 2011, Evidence for the “protein-only” Hypothesis—Fungal prions and Prion proteins

13/10/2012 · What was the proteins first hypothesis ..

In 2001, our group developed a technique to replicate prions in vitro, termed Protein Misfolding Cyclic Amplification (PMCA). PMCA improved the efficiency of prion conversion over the pioneer work of Caughey with the cell-free conversion process,, enabling to test the infectious properties of in vitro generated PrPSc. Considering the many failures on the attempts to produce infectious folding from rPrP, we hypothesized that this conformation must be very special and thus we attempted to mimic the pathological process of prion formation in the test tube. PMCA was shown to reproduce the auto-catalytic replication of prions in a greatly accelerated manner. The in vitro-generated material was shown to keep all the biological, biochemical and structural characteristics of in vivo produced prions. More importantly, we showed for the first time the production of bona-fide infectivity in wild type animals. Recently, we have shown that different prion strains can retain their properties with high fidelity after many passages in PMCA. Furthermore, more complex processes, such as species barrier crossing and strain adaption, were recreated in our lab using this technology., These findings indicate that infectivity and associated properties (strain variability, species barrier and strain adaptation) are purely dependent on the formation of PrPSc, which can be done in a cell-free system, thus ruling out the involvement of genetic material.