In article <92237.151615FORSDYKE at QUCDN.QueensU.CA> <FORSDYKE at QUCDN.QueensU.CA> writes:
>> physiologists to explain Donnan equilibrium. Now, if these
> collective functions were important from the viewpoint of
> evolutionary selection, then genes would be modified based on
> selection for these functions.
I think this would be hard to argue from an evolutionary standpoint, because
evolutionary changes usually, if not always, refer to modifications in
protein function. With hundreds (or thousands) of different proteins in a cell
it is difficult to imagine how all these proteins would evolve, with
consideration of all the others, to reach a certain final ?isotonicity? in
the cytosol. And remember, proteins are not just generic chains of amino
acids. There are hydrophilic and hydrophobic, abd they also vary in charge.
All of these interactions, and more, must be included in your model.
> thus begin to define "self". The particular property of interest
> is that of protein concentration. Throughout evolutionary time
> each gene "fine-tunes" its protein concentration to the collective
> pressure exerted by the other proteins with which it is moving
> through time. At the same time, all the proteins tend to maximize
> the collective pressure to drive individual proteins from solution,
> by pushing their own concentrations to the limit. In this
> cytosolic environment, a not-self protein might more readily
> exceed its individual solubility limits. Thus is would aggregate
> and mark itself as foreign, thus fulfilling the criterion
> advanced earlier for its being conducted, via proteosomes, to the
> MHC protein complexes.
> This is not the end of the story. There are some flaws to this
> argument. Perhaps you can spot them, and others that I have not
> noted?
> Sincerely, Don Forsdyke
Where is the "right" protein concentration determined? For those that are
compartmentalized, is the proper concentration determined while they are
being synthesized on the free ribosomes, or when they have reached their
final compartment?
As stated above, it is easier to see how evolution determines
protein function, by comparing various species of the same protein, e.g.
cytochrome c. Although it may be logical, it is more difficult to
experimentally determine how evolution determines the final protein
concentration. Are there any references on this?
As far as virla protein solubility limits, viruses too are highly evolved
to be as efficient as possible. With a rapidly lytic virus, it could care
less about staying below the solubility limits, as its goal is to produce
viral proteins, package its nucleic acid, and lyse the cell, all before
an immune response can destroy the infected cell. Other viruses have
different mechanisms of controlling protein expression so that the host
cells are not lysed quickly, or do not become targets.
If a certain virla protein exceeds its solubility limit, then it may be at
a concentration that outcompetes self proteins for MHC binding. Calling
overexpression a form of self-nonself discrimination seems really to be a
situational use of the term, i.e it applies only in those cases where the
nonself protein exceeds the self protein. In the case of a slow, or latent
viral infection, where the foreign proteins are not present at high levels,
they would not aggregate, and in fact mimic the "self."
This type of self-nonself discrimination does not exclude self proteins
from presentation. For example (forgive me for forgetting the correct names
of the mutants) observations with the ?RAS? cell line has led to the
following conclusions:
1. Class I-peptide complexes are more stable that class I alone.
2. The stability of empty class I is increased by lowering the
temperature.
3. Therefore stable class I complexes, at the cell surface, need
a peptide bound to the groove.
Now what we consider "normal" is the class I expression of an uninfected
cell. These cells express class I about 20 times as much as the RAS mutant.
Since these cells are uninfected by any virus that produces large amounts
of its proteins, the only way to achieve stable class I expression would
be to complex it with self peptides. This also serves the function (by the
current "dogma") of protecting the cell from lysis by NK cells - presumeably
NK cells recognize the LACK of class I on the surface as their "target."
Comments? Arguments? Discussion?
Shiv
>>>>>>>>>>> Prasad, S. (1992) Bionet.immunology 814 1516gmt
>>>>>>>>>>> Forsdyke, D. (1992) Bionet.immunology 817 1757edt
>>>>>>>>>>> Prasad, S. (1992) Bionet.immunology 818 133gmt
>>>>>>>>>> Forsdyke, D. (1992) Bionet.immunology 818, 1616edt
>>>>>>>>> Prasad, S. (1992) Bionet.immunology 819, 405gmt
>>>>>>>> Forsdyke, D. (1992) Bionet.immunology 819 1019edt
>>>>>>>> Prasad, S. (1992) Bionet.immunology 819, 2019gmt
>>>>>> Forsdyke, D. (1992) Bionet.immunology 820, 858edt
>>>>>>> Prasad, S. (1992) Bionet.immunology 821, 56gmt
>>>> Forsdyke, D. (1992) Bionet.immunology, 821, 858edt
>>>> Prasad, S. (1992) Bionet.immunology 821, 1544gmt
>> Forsdyke, D. (1922) Bionet.immunology 824, 918edt
>> Prasad, S. (1992) Bionet.immunology 824, 1814gmt
Forsdyke, D. (1992) Bionet.immunology 824, 1416cdt
(Sorry, I accidentally deleted some of the earlier references)
