Regulatory Proteins

by Georgina Cornwall, PhD

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    00:01 Now that you are clear on the mechanisms of gene expression, let us talk about how it is regulated. By the end of this lecture, you should be able to recognize the most common DNA binding motifs as well as explain how an inducible operon functions and explain how a repressible operon functions. We are addressing prokaryotic gene regulation as well as different binding motifs. Let us begin by looking at DNA structure in brief. We have a double-stranded helical DNA molecule, something we haven't talked about is how the size of this works out. Each turn of the helix is about 3.4 nanometers in length and there are 10 base pairs per turn, which means that each base pair distance is about quite 0.34 nanometers apart. The way that the helix happens in the alpha-helical form is we have a major groove where it is wider spacing between the phosphate, sugar backbones and a minor groove where things are much closer together. Previously it was thought that DNA would have to unwind its helical form in order to allow access of the regulatory proteins and polymerase in such that are involved in gene expression. However, now we recognize that this major groove actually gives fairly good access to the base pairing of the nitrogenous bases. And in this figure you can see the three hydrogen bonds that we see between the G and C nucleotides and when we are in the major groove, it is fairly open and so many of the enzymes involved in DNA transcription can actually access that zipper and open it up.

    02:00 Similarly, when we are more in the major groove above the A and T, you can also see the two bonds and those can be accessed. The major groove provides great access for enzymes to work on DNA when it is not completely unwound and let us say flattened out. Knowing that we need to look out how these proteins bind to DNA. There are a few main binding motifs or patterns of binding that come up quite frequently in genetics and gene expression.

    02:35 Here are three helix-turn-helix, zinc fingers, and leucine zippers.

    02:40 We will begin looking at the helix-turn-helix motif. This involves a helix in the one domain of the protein. Let us start by each of these regulatory proteins is different in structure.

    02:54 However, they have a binding domain that actually helps them attach to the DNA so that they can do the jobs that they need to do. In this helix-turn-helix motif, the pattern is to have two helixes that are perpendicular to each other and they have a loop of nonhelical protein structure in between them. Generally in the helix-turn-helix motif, we see that there are two sets of these perpendicular segments and they have sort of a symmetrical pairing in order to anchor the whole protein onto the DNA, so that that enzyme can do whatever that is supposed to do. Helix-turn-helix is a very common binding domain or motif and we can look specifically at homeodomain proteins and I addressed this one because the idea of homeodomain binding motifs will come up fairly frequently because homeodomain binding proteins seem to be displayed in developmental regulatory processes.

    04:06 You might hear in the literature, lots of things about homeodomain and this is a modification of the helix-turn-helix motif in which you see these helical structures of the homeodomain portion lining in the major groove. There is extra helix and then the rest of the protein that is involved in transcription activation is located away from that. In the same way, that other helix-turn-helix, or zinc finger, or whichever another binding motif we use, we have the domain that is integrating into the DNA and holding on and then we have the rest of the protein that does its function. Homeodomain proteins are just a specific kind of anchoring point using the helix-turn-helix motif. So next, the zinc finger motif, literally kind of like three fingers going into the DNA to hold onto it. They use zinc in order to associate with DNA and so these fingers will actually integrate into the DNA and hold on in the sort of fashion using the major groove and one place we have seen these in action already. It is with the action of the steroid receptor. We call that steroids bind to the receptors inside the cell and often inside the nucleus and those receptors bind directly to the DNA.

    05:36 Those receptors actually have a protein subunit, which is the zinc finger binding motif mechanism holding it onto the DNA so that they can work in adding to the transcription rate of DNA at that region. Now let us look at the leucine zipper. This is a pretty cool arrangement too where we are also using the major groove on the DNA.

    06:04 The leucine zipper motif has two subunits. One going in each direction and a portion of each subunit is hydrophobic and thus doesn't want to be close to the DNA, but it has a bunch of leucines on it that hold it together and that is the zipper part. And then the other subunit of each of these pieces is a helical form, which sits in the major groove. They usually sit in the major groove in opposite directions literally anchoring the leucine zipper right in place. Again other pieces of the protein, other domains of the protein will go ahead and do the jobs that they do now that they are attached to the DNA. The

    About the Lecture

    The lecture Regulatory Proteins by Georgina Cornwall, PhD is from the course Gene Regulation.

    Included Quiz Questions

    1. Zinc finger motif
    2. Helix-turn-helix motif
    3. Leucine zipper
    4. Greek key
    1. Homeobox genes ----- Controlled by leucine zipper
    2. Leucine zipper ----- Eukaryotic transcription factors
    3. Helix-turn-helix motif ----- Two perpendicular α- helical segments
    4. Zinc finger motif ----- Coordination of zinc ions to bind with DNA
    5. Homeodomain ----- Play major roles in many developmental processes of eukaryotes
    1. …regulate the expression of other genes in development and differentiation of the eukaryotes.
    2. …regulate the expression of DNA replication regulating genes in the eukaryotes.
    3. …regulate the expression of DNA repair regulating genes in the eukaryotes.
    4. …regulate the expression of cell cycle regulating genes in the eukaryotes.
    5. …regulate the expression of cell death regulating genes in the eukaryotes.

    Author of lecture Regulatory Proteins

     Georgina Cornwall, PhD

    Georgina Cornwall, PhD

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