Doesn't natural selection act like a Reverse Translatase? Which is
quite an elegant implementation of the idea...
On Sep 7, 2010, at 6:29 PM, Artem Evdokimov wrote:
> Regardless of whether a system like this exists in Nature or not -
> it's fun to imagine!
>
> On a microscopic scale one could propose a hypothetical mechanism by
> which a completely unfolded polypeptide chain could be fed into a
> gated (or state-locked) peptidase that may break the chain down in a
> co-ordinated stepwise fashion; releasing individual aa's into some
> sort of a nanoscale channel. The released aa's would then be
> sequentially coupled to something resembling tRNA - with pre-formed
> trinucleotides attached on the other end. Coupling would then
> presumably permit the triplets to ligate to one another sequentially -
> the resulting ssDNA or ssRNA would then have to be converted into a
> stable ds-form via the usual means, or otherwise protected in one of
> the usual ways. Codon space could be expanded by pre-loading carrier
> molecules with more than one type of triplet per carrier (biased
> towards whatever codon frequencies are prominent in the organism of
> choice) although this in no way resolves the random nature of the
> actual codon use within the resulting nucleotide sequence.
>
> The issue of amino acid coupling selectivity is pretty hairy - the
> best I could think of on a short notice is to have the receptor sites
> for individual aa's arranged in order of dropping selectivity --
> however there is still the matter of shape/property similarities
> throwing wrenches into the works. An alternative would be a series of
> binary gates working on an exclusion principle.
>
> As to practicality of this kind of stuff - I am not sure; I can
> imagine an application similar to nano-scale multiparallel
> pyrosequencing: an unknown protein would be broken down into peptides
> via nonselective protease of some sort and then relatively short
> individual peptides are 'sequenced' in parallel, producing short DNA
> sequences that would later be complemented to dsDNA and allowed to
> cross-anneal and self-assemble via overlaps, similar to gapped gene
> assembly from short synthetic fragments (that first protease better be
> *really* non-specific!). At the end one could sequence the resulting
> long DNA to see what the original protein was like.
>
> A.
>
> On Tue, Sep 7, 2010 at 8:35 AM, David Schuller <[log in to unmask]>
> wrote:
>> On 09/06/10 21:36, Jacob Keller wrote:
>>>
>>> Dear Crystallographers,
>>>
>>> does anyone know of any conceptual reason why a reverse
>>> translatase enzyme
>>> (protein-->nucleic acid) could not exist? I can think of so many
>>> things
>>> for
>>> which such an enzyme would be helpful, both to cells and to
>>> scientists...!
>>> Unless there is something I am missing, it would seem to me
>>> conceptually
>>> almost impossible that it *not* exist.
>>
>> See: "The RNA/Protein Symmetry Hypothesis: Experimental Support for
>> Reverse
>> Translation of Primitive Proteins"
>> Masayuki Nahimoto, J. Theor. Biol. (2001) 209, pp 181-187.
>>
>> In which Nahimoto proposes such a system, and additionally proposes
>> that it
>> actually existed early in the development of life on this planet.
>>
>> Reasons why it "could not exist" - No. Reasons why it would be very
>> difficult - yes. And plenty of reasons why Nahimoto is probably
>> wrong about
>> it having actually existed:
>>
>> There is absolutely no evidence presented that such a system was
>> ever in
>> operation in the history of life on this planet.
>>
>> Current theories such as the RNA World are much more likely
>> explanations for
>> how life as we currently know it may have developed from a pre-
>> biotic state.
>>
>> DNA replication, DNA=>RNA transcription, and RNA=>Protein
>> translation all
>> depend on nucleic acid base pairing for part of their specificity.
>> It truly
>> is the secret of life. And it would not be especially helpful in
>> Protein=>RNA reverse translation.
>>
>> Forward translation takes place in the ribosome, but extra
>> specificity is
>> "smuggled in" via a large set of tRNAs and tRNA charging enzymes, in
>> reactions which took place beforehand, which are then made use of
>> through
>> the base-pairing codon:anti-codon recognition.
>> Reverse translation would most definitely not be running forward
>> translation
>> in reverse;
>> the specificity cannot be handled ahead of time, it needs to be
>> available at
>> the site of reverse translation itself when each successive peptide
>> residue
>> is presented.
>>
>> Progressivity: If different recognition sites are swapped in, this
>> has to be
>> done while keeping place in both the protein chain and in the growing
>> nucleotide chain. Possibly the protein chain might be cleaved
>> during the
>> process. The chemistry and geometry of peptide residues is far more
>> variable
>> than that of nucleotide residues.
>>
>> The genetic code of reverse translation would be completely
>> independent of
>> that in forward translation. For the two to have matched up (in the
>> proposed
>> naturally occurring RT system) would have been extremely fortuitous,
>> imposing a strong barrier to the introduction of such a system.
>>
>> Difficulty in dealing with post-translational modifications
>> disulfides,
>> cyclical peptides, acetylation, phosphorylation, etc.
>>
>> A peptide sequencer coupled with a nucleotide synthesizer
>> accomplishes
>> somewhat the same thing, but on a macroscopic scale. This is an
>> impediment
>> to the motivation for constructing a reverse translatase enzymatic
>> system.
>>
>> Cheers,
>>
>> --
>> =
>> =
>> =====================================================================
>> All Things Serve the Beam
>> =
>> =
>> =====================================================================
>> David J. Schuller
>> modern man in a post-modern world
>> MacCHESS, Cornell University
>> [log in to unmask]
>>
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