Date: Thu 11 Jan 2001 07:56:41 EST
From: Terrence O'Neil, MD, FACP <Tjon1950@aol.com>
Phenotypic Susceptibility May be the Key
----------------------------------------
Prions have been discovered across families and even phyla. Prion-like
proteins have been identified in [yeast, fungi] and mammals. They must be
there for a reason, and as chaperonins they could confer an ability to
alter the quaternary conformation of a single protein into different
functional shapes.
This would serve to enlarge the range of catalytic options open for a
single polypeptide [chain] generated by a single nucleotide sequence into a
variety of potentially useful functions. This would also convey adverse
selective advantage if a given chaperonin operating on a given polypeptide
resulted in a conformation with a lower free energy in the crystalline form
than in aqueous solution. Such proteins would only occur when a specific
chaperonin operated on a specific polypeptide [chain].
Relatively minor alterations in the amino acid sequence might result in
sufficiently different final 3-D conformations for one variant to avoid
self-assembly into ubiquitin-resistant protein tangles. Hence, given
members of a single family with slightly different proteins might be
susceptible to ingestion of a particular prion resulting in disease, and
others not. The resulting spottiness of clinical expression could obscure
the epidemiology sufficiently to confuse those doing case surveillance.
The possibility exists that prions, as chaperonins, have been around for a
long time in many species, susceptible to selective pressures the same as
any other proteins, with our discovery of them coming only after human
intervention in the food chain introduced a new condition: herbivores
consuming herbivores in artificial feed. If such introduction of prions
which had been selected by evolution to not cause self-assembly of other
proteins in the organisms resulted in self-assembly of specific proteins in
a distantly-related species, the result would be pathology. This is a
fascinating concept, which should be amenable to systematic confirmation or
negation.
--
Terrence O'Neil, MD, FACP
US Air Force, Medical Corps
<Tjon1950@aol.com>
A ProMED-mail post
http://www.promedmail.org
ProMED-mail, a program of the
International Society for Infectious Diseases
http://www.isid.org