Re: tRNA, ribosomes, and codons

Dear Alex,

This is a great question. I think that you will find that the answer points 
out that many of the insights that we gain from handling everyday objects 
around the house or while playing baseball do not apply very well to 
molecules. For example, if you want the third volume of the encyclopedia 
back on the shelf where it belongs, you or the librarian are going to have 
to pick it up and put it there. Why should a charged tRNA be any different?

This is explained in a really cogent way in The Molecular Biology of the 
Cell by Alberts et al., available online. The relevant part of the book is 
"Molecular Recognition Processes" in Chapter 3, specifically:
 http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?tool=bookshelf&call=
bv.View..ShowSection&searchterm=small&rid=cell.section.d1e5024#d1e5473

(If you go to the online book, you will be able to see the figures and 
references.)

To quote, in part:

________

"Diffusion Is the First Step to Molecular Recognition 4 

Before two molecules can bind to each other, they must come into close 
contact. This is achieved by the thermal motions that cause molecules to 
wander, or diffuse, from their starting positions. As the molecules in a 
liquid rapidly collide and bounce off one another, an individual molecule 
moves first one way and then another, its path constituting a "random walk" 
(Figure 3-7). The average distance that each type of molecule travels from 
its starting point is proportional to the square root of the time involved: 
that is, if it takes a particular molecule 1 second on average to go 1 um, 
it will go 2 um in 4 seconds, 10 um in 100 seconds, and so on. Diffusion is 
therefore an efficient way for molecules to move limited distances but an 
inefficient way for molecules to move long distances.

Experiments performed by injecting fluorescent dyes and other labeled 
molecules into cells show that the diffusion of small molecules through the 
cytoplasm is nearly as rapid as it is in water. A molecule the size of ATP, 
for example, requires only about 0.2 second to diffuse an average distance 
of 10 um - the diameter of a small animal cell. Large macromolecules, 
however, move much more slowly. Not only is their diffusion rate 
intrinsically slower, but their movement is retarded by frequent collisions 
with many other macromolecules that are held in place by molecular 
associations in the cytoplasm (Figure 3-8).

Thermal Motions Bring Molecules Together and Then Pull Them Apart 4 

Encounters between two macromolecules or between a macromolecule and a small 
molecule occur randomly through simple diffusion. An encounter may lead 
immediately to the formation of a complex between the two molecules, in 
which case the rate of complex formation is said to be diffusion-limited. 
Alternatively, the rate of complex formation may be slower, requiring some 
adjustment of the structure of one or both molecules before the interacting 
surfaces can fit together, so that most often the two colliding molecules 
will bounce off each other without sticking. In either case once the two 
interacting surfaces have come sufficiently close together, they will form 
multiple weak bonds with each other that persist until random thermal 
motions cause the molecules to dissociate again (see Figure 3-3).

In general, the stronger the binding of the molecules in the complex, the 
slower their rate of dissociation. At one extreme the total energy of the 
bonds formed is negligible compared with that of thermal motion, and the two 
molecules dissociate as rapidly as they came together. At the other extreme 
the total bond energy is so high that dissociation rarely occurs. Strong 
interactions occur in cells whenever a biological function requires that two 
macromolecules remain tightly associated for a long time - for example, when 
a gene regulatory protein binds to DNA to turn off a gene. Weaker 
interactions occur when the function demands a rapid change in the structure 
of a complex - for example, when two interacting proteins change partners 
during the movements of a protein machine."

________

What this means is that the ribosome's A site is being bombarded with 
charged tRNAs, driven by thermal diffusion, at a rate that is difficult for 
you to imagine. Most of the time, either no interactions occur, or any 
interaction that does occur is weaker than the thermal energy dissociating 
the tRNA from the ribosome. Rarely, the right charged tRNA hits the A site, 
and the multiple hydrogen bonds in the codon-anticodon interaction stabilize 
the interaction. So you have already guessed the essence of this answer in 
your suggestion that all of the tRNAs in the cytoplasm attempt to fit.

This answer might at first seem unsatisfactory, but consider the 
alternative: that there is something in the cell that reads the codon, then 
goes looking for the right charged tRNA to bring it over and put it into the 
A site. That isn't a simpler explanation than the one I have given, even 
though your everyday experience tells you that Volume 3 of the encyclopedia 
is going to require you or the librarian to get back on the shelf.

Yours,

Paul Szauter