What is life, anyway, and do prions have anything to do with the
abiogenesis problem?
5. MEDICAL BIOLOGY:
EXPERIMENTAL EVIDENCE SUPPORTING THE PRION HYPOTHESIS
In general, the "prion hypothesis" postulates that a protein
(prion), by virtue of its ability to propagate in an altered
conformation, can act as an infectious agent.
Prions are apparently infectious agents that lack nucleic
acid and are composed of a *beta-sheet-rich altered conformation
of a normal cellular protein. Prion infectivity is believed to
result from the ability of the prion protein in its altered
conformation to bind to the normal form of the protein and
catalyze the conversion of the normal protein to the infectious
conformation.
While originally identified as the causative agent for a set
of related transmissible spongiform encephalopathies, including
Cruetzfeldt-Jacob disease in humans, scrapie in sheep, and "mad
cow disease" in cattle, self-propagating beta-sheet-rich protein
aggregates also underlie a variety of noninfectious
neurodegenerative diseases. These include the relatively common
disorders Alzheimer's disease and Parkinson's disease, as well as
inherited polyglutamine repeat disorders such as Huntington's
disease. [For more on the above pathologies, see related
background material below.]
... ... H.E. Sparrer et al (4 authors at University of California
San Francisco, US) report experimental evidence supporting the
prion hypothesis, the authors making the following points:
1) In addition to a role in human pathogenesis, beta-sheet-
rich aggregates of glutamine and asparagine-rich domains mediate
inheritance of certain prion-like traits ([PSI+] and [URE3]) in
the yeast Saccharomyces cerevisiae, and the easily manipulated
genetics of this organism has made yeast prions a rich source of
information concerning the mechanism of prion propagation in vivo
as well as the role of prion-based inheritance in the normal
physiology of a cell.
2) Starting with purified, bacterially produced protein, the
authors created a yeast prion-like trait- ([PSI+]) inducing
agent, the agent based on an altered (prion) conformation of a
yeast protein (Sup35p). After converting this protein to its
prion conformation in vitro, the authors introduced it into the
cytoplasm of living yeast, and this resulted in a greatly
increased rate of appearance of the well-characterized prion-like
trait, which is known to result from self-propagating aggregates
of the altered form of the cellular protein Sup35p [*Note #1].
The authors state: "Thus, as predicted by the prion hypothesis,
proteins can act as infectious agents by causing self-propagating
conformational changes."
3) In a commentary on the above work, Mick F. Tuite
(University of Kent Canterbury, UK) states: "[Sparrer et al] show
that the prion form of the normal yeast protein Sup35p
effectively seeds a self-propagating conformational change in
normal Sup35p of living yeast cells. Their demonstration provides
the finishing touches to an extensive body of data that supports
the protein-only hypothesis."
-----------
H.E. Sparrer et al: Evidence for the prion hypothesis: Induction
of the yeast [PSI+] factor by in vitro-converted Sup35 protein.
(Science 28 Jul 00 289:595)
QY: Jonathan S. Weissman [jsw1@itsa.ucsf.edu]
-----------
Mick F. Tuite: Sowing the protein seeds of prion propagation.
(Science 28 Jul 00 289:556)
QY: Mick F. Tuite [m.f.tuite@ukc.ac.uk]
-----------
Text Notes:
... ... *beta-sheet: In general, protein chains fold into
alpha-helices or beta-sheet structures. The beta-sheet is a
protein structure where the peptide is extended and stabilized by
hydrogen bonding between NH and CO groups of different
polypeptide chains or of separate regions of the same chain.
... ... *Note #1: The normal form of the protein Sup35p is
essential for decoding *messenger RNA (mRNA) in yeast. The normal
protein is hydrolyzed by *protease and does not aggregate. The
functionally inactive prion form of Sup35p confers the so-called
[PSI+] *phenotype on yeast cells. In such strains of yeast,
Sup35p is found almost exclusively as a protease-resistant, high
molecular weight-aggregate.
... ... *messenger RNA (mRNA): The ribonucleic acid molecule
transcribed from DNA that carries the coded information
specifying the sequence of amino acids in a protein.
... ... *protease: In general, any enzyme that cleaves proteins,
usually by hydrolysis.
... ... *phenotype: In general, term "phenotype" refers to the
organism as determined by the interaction between its genetic
constitution (genotype) and the environment.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 11Aug00
For more information: http://scienceweek.com/swfr.htm
-------------------
________________________________________________________________
YOU'RE PAYING TOO MUCH FOR THE INTERNET!
Juno now offers FREE Internet Access!
Try it today - there's no risk! For your FREE software, visit:
http://dl.www.juno.com/get/tagj.
This archive was generated by hypermail 2b29 : Wed Aug 09 2000 - 00:00:21 EDT