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The Common Arm Digest; issue #3:
Ratchet Redux
FolksI want to consider the Yonath symmetric dimer core (of the 50S
ribosome) in relation to Woese's old Reciprocating Ratchet (also
symmetric).
The notion that symmetry lies at the heart of translation -- both within
and between tRNA molecules (in translation) and at the core of the
ribosome (defined by the peptidyl-transfer center) is an hypothesis
of major import. [The adjective "major" is used here because the
implications of the notion transcend translation per se; going into the
dynamic of the mechanism's evolution; beyond that into the evolution
of (all or most) biological macromolecules; then to the evolution of
biological entities (and processes?) at all its organizational levels; and
(see CAD issue #2) finally into the evolutionary nature of the Universe
itself (not to put too fine a point on it).
If the peptidyl transfer center be symmetric, we can -- perhaps should
-- expect symmetry to be manifested as well in the passage of the
tRNAs through the mechanism. [The crystal structure models of
tRNAs in the ribosome need to be taken with a grain of salt if they fail
to show any symmetry in the "tRNA passage" in translation.] I had
originally assumed the 23S rRNA (and so 50S particle) had a two-fold
symmetry (based mainly on a faulty report that the modified bases in
23S rRNA were each present in 2 copies). This had led to the
suggestion (which I came to regret) that translation was a "parallel
processl -- in the sense that say, the even numbered codons were
processed through one translation site on the 50S particle, their odd
numbered counterparts through a second site (which symmetry would
demand). Fortunately, this "gross mechanical" aspect was not the
essence of the Ratchet model.
Now, I begin to wonder. Could this have been the wrong ratchet for
the right reason? Could the common arm be involved in some kind of
ratcheting symmetry? In any case, let's mark the Common Arm (and
possible allosteric transitions therein) for special attention as we
study and refine the 3D model of translation in process.
It is so satisfying, both esthetically and personally, to see the shift in
thinking among the lumpen molecularists/ crystallographers, from an
r-protein focus to an r-RNA (and soon perhaps also tRNA) focus in
modeling the mechanism of translation.
Carl
PS: in summary: does the Common Arm in some sense rotate
symmetrically in relation to the symmetric center in the 50S particle,
in “translocation”?
Also, is it possible to speak at all (precisely) of primary structural homology
when dealing with statistical proteins?. For small enough polypeptides one
may start out with (representatively speaking) “all” possible sequences
consistent with given higher order structural constraints—either in molecular
folding and/or the translation mechanism itself. I think the constraints had to
come largely from the primitive translation mechanism to begin with. In the
beginning the translation mechanism had to have been the “ultimate node in
the net”.
The easiest way to get order into protein sequence I used to think (and still
do, but haven’t paid it much attention) is to alternate between two tRNAs
whose “anticodon” arms are complementary to one another. No message,
but you still get order in the form of a peptide whose primary structure
alternates between two amino acids. Too innocent a thought, however.
What about it’s higher order structure? Could it have any functional
significance? Not likely. But, as Orgel suggested such could form beta
sheet membrane proteins; and as I later said, an alternating basic-other
polypeptide could structure a single strand of DNA as though it were double
stranded.