How Do tRNA Anti-Codons Find the Right mRNA Codons So Quickly?

[stfaivus]

given humans have 64 possible codons, I am imagining a crowd of tRNA, each carrying an amino acid, swarming clumsily with random thermal motion around a ribosome with a feed of mRNA. How do the tRNA anti-codons find the right mRNA codons so quickly?! I saw a video that shows the amino acids zipping together at about the speed of zipping up a zipper. Based on random thermal motion and the crowd with great variety of anti-codons, making the right match so quickly seems impossible. I know there are protein catalysts involved, but...?

 

[epenguin]

given humans have 64 possible codons, I am imagining a crowd of tRNA, each carrying an amino acid, swarming clumsily with random thermal motion around a ribosome with a feed of mRNA. How do the tRNA anti-codons find the right mRNA codons so quickly?! I saw a video that shows the amino acids zipping together at about the speed of zipping up a zipper. Based on random thermal motion and the crowd with great variety of anti-codons, making the right match so quickly seems impossible. I know there are protein catalysts involved, but...?

that's it I think.

 

[Ryan_m_b]

given humans have 64 possible codons,

For only 20 amino acids. This is a buffer against deleterious mutation.

I am imagining a crowd of tRNA, each carrying an amino acid, swarming clumsily with random thermal motion around a ribosome with a feed of mRNA. How do the tRNA anti-codons find the right mRNA codons so quickly?! I saw a video that shows the amino acids zipping together at about the speed of zipping up a zipper. Based on random thermal motion and the crowd with great variety of anti-codons, making the right match so quickly seems impossible. I know there are protein catalysts involved, but...?

That's pretty much how it works. In videos the soup of other biochemicals constantly present in a cell is cut out and molecules are shown mysteriously swimming towards each other. Even with mechanisms that aid reactions (e.g. Protein complexes that move molecules from A to B once attached) there is an element of molecules moving around "randomly" until they meet. But this isn't a problem because of how small a cell is, how fast molecules can move and how many reactions tend to happen at once.

 

[mishrashubham]

Based on random thermal motion and the crowd with great variety of anti-codons, making the right match so quickly seems impossible.

Yes it's really fascinating. It's sometimes hard to imagine how random collisions result in such a quick reaction but then it is equally hard for us to imagine how fast these molecules move and the kinds of energies they have. And the catalyst doesn't actually pull it closer or help it find it's way to the required site (although some enzymes actually do that, amazing isn't it?); the molecules still have to collide (see Collision Theory) in order to react, the catalyst just makes sure that it doesn't have to hit as hard (or in other words decreases the activation energy).

 

[stfaivus]

Can someone help with working out the figures here? I want to find approximate values for the mass of a tRNA loaded with an amino acid, the mean speed of that loaded tRNA in a typical temperature around the ribosome, and the mean distance between collisions, or free mean path, between all the stuff floating around the ribosome. What I ultimately am interested in is how many times a particular loaded tRNA would collide with the loaded mRNA at the ribosome per second. As I think about this, it still seems impossible to join amino acids/synthesize protein so quickly!

 

[Ygggdrasil]

You may be able to find these numbers at the following site: http://bionumbers.hms.harvard.edu/KeyNumbers.aspx

tRNAs have a mass of about 25 kDa, which is comparable to that of some small proteins, whose diffusion limited collision rate is ~10⁸-10⁹ M^-1s^-1 in cells. I estimate that in bacteria the total concentration of tRNA is ~100µM. Assuming that only a small fraction of that pool of tRNAs represents the correct tRNA (let's go with 1%), I estimate that the the diffusion-limited reaction rate of the ribosome is ~100-1000 s^-1, well above the observed translation rate of 10-20 s^-1.

 

[stfaivus]

when you write tRNA have a mass of about 25 kDa, is this a tRNA loaded with an amino acid? The Harvard bionumber website gives average amino acid in E. coli as 109 kDa, so it seems the loaded tRNA would be a lot more massive than 25 kDa. Also, the rate is not simply when the correct tRNA hits the mRNA. Doesn't it have to hit at just the right place, the place with the exposed anti-codon? Do the helper proteins help to orient the tRNA as it hits the mRNA?

 

[Yanick]

Amino acids are on average about 110 Da. Proteins, made of many amino acids, are in the kDa range. You are off by a few orders of magnitude of the MW of an amino acid.

 

[stfaivus]

Thank you.