|MadSci Network: Cell Biology|
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
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