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Lecture 7

Cell Biology - Lecture 7 - Video 2.1 - Notes

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CAS BI 203
Martin Steffen

Lesson 7 – Video 2a [00:00:00.00] 79 [00:00:01.67] SPEAKER: Hi. In this video, we'll 2867 continue our discussion on Gene Specific 2868 Transcription. In particular, we're going to focus most of this lecture on the Trp repressor. Trp is 2869 short for tryptophan, the amino acid.And we're going to talk about negative feedback, which 2870 we've already seen with enzymes.And again, allostery is going to play the key role in terms of a 2871 small molecule binding to a protein, changing its shape, which then changes the proteins 2872 function. 2873 [00:00:32.18] We'll look at more complex mechanisms of gene regulation. In particular, we'll 2874 look at the way the cells decide which sugar to use.And then we'll look at some other complex 2875 mechanisms. So here is the operon for tryptophan bio synthesis. There are five genes that make 2876 five proteins that each play a different role in the bio synthesis of this amino acid; amino end, 2877 alpha carbon, carboxylic end, and then the big side chain here. 2878 [00:01:11.29] These five genes are coordinately regulated since this is an operon, it's a 2879 polycistronic mRNA. They are all regulated by this promoter region. With the idea that if you 2880 need to make one of these enzymes, you need to make all of them. Because there's not much use 2881 in going part of the way to making the tryptophan molecule, but not completing the task. 2882 [00:01:35.25] In this example, the cells default state is that the genes are turned on if the 2883 promoter region is empty, RNApolymerase will bind to the promoter region, and start making 2884 the mRNA tryptophan bio synthesis. Since tryptophan is going into every protein that's made, it's 2885 important to have a lot of it. So the default decision for the cell is to have the gene turned on. 2886 [00:02:03.14] But what happens when you have too much tryptophan when you've already made 2887 a lot and you don't need more? In that case, tryptophan binds to the Trp repressor protein right 2888 here.And will induce a confirmation, here it's rounded in a won't bind DNA. When the repressor 2889 binds to the protein, it changes its conformation. It's now able to bind DNAin the place where 2890 RNApolymerase normally binds and so that the genes are turned off. 2891 [00:02:37.80] So this is a very simple example of negative feedback regulation. Here the default 2892 state is, let's make more tryptophan. The negative feedback is, hey, we've got too much 2893 tryptophan, stop for a little bit.And this all happens automatically since the molecule being made 2894 is also the molecule that binds to the repressor to induce the conformational change. 2895 [00:03:03.54] On this slide, we see a bit of the detail of the repressor bound to DNA. Let's look 2896 first at the case where the genes are off, where the repressor is bound to DNA. You see this is a 2897 symmetrical protein. You can see that helix is perfectly positioned to bind to the major groove 2898 here.And a second helix is binding to a second major groove here.And the spacing between 2899 these two arms is just appropriate for sitting down and having those both spaced properly.And 2900 you can see the tryptophan here is sort of in a hinge region.And you can see that
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