Question

Tyrosine kinase receptors are pairs of proteins that span the plasma membrane. On the extracellular side of the membrane, one or more sites are present that bind to signaling ligands such as insulin or growth factors. On the intracellular side, the ends of peptide chains on each protein phosphorylate the other member of the pair, providing active docking sites that initiate cellular responses. The signal is switched off by dissociation of the ligand. For each ligand-receptor system, the equilibrium constant, k, controls the distribution of receptor-bound and unbound ligands. In systems with large values of k, a site is likely to be occupied, even at low concentrations of ligand. When k is small, the likelihood of binding is low, even when the concentration of ligand is high. To initiate a new stimulus response cycle for the receptor, the ligand must dissociate. Larger values of k mean that the receptor is more likely to be occupied and thus unavailable to bind another ligand. Some ligand-binding systems have multiple binding sites. For example, hemoglobin binds four oxygen molecules, whereas myoglobin has only a single binding site. When multiple binding sites are present, the presence of an already-bound ligand can cooperatively affect the binding of other ligands on the same protein. For hemoglobin, the binding is positively cooperative. The affinity of oxygen for heme increases as the number of bound oxygen molecules increases A. Describe the features in the graph above for hemoglobin that demonstrate positive cooperativity. B. The insulin receptor (IR) is a tyrosine kinase receptor that has two sites to which insulin can attach. IR is negatively cooperative. In the diagram above, the dependence of the bound fraction on available insulin is similar to the curve for k = 1 with negative cooperativity. Describe the features of this curve in the graph above that demonstrate negative cooperativity. C. When viewed from above the cell-surface, the representation shows receptors with one and two bound insulin molecules. Explain the negative cooperation for this receptor based on the free energy of conformational changes in the receptor-peptide chains. D. (Can't copy) E. Explain the advantages in terms of selection of two-site binding with negative cooperation relative to one-site binding. F. Three binding curves with negative cooperativity and different values of k are shown on the graph. Describe conditions in which there is an advantage in having a low value of k with negative cooperativity.

Name: Problem 44, Chapter 9: Biology for AP Courses
Uploaded: 2019-07-26T17:30:30-08:00
Duration: 8 min 46 s
Channel: Bryan Lynn

A. Describe the features in the graph above for hemoglobin that demonstrate positive cooperativity.
B. The insulin receptor (IR) is a tyrosine kinase receptor that has two sites to which insulin can attach. IR is negatively cooperative. In the diagram above, the dependence of the bound fraction on available insulin is similar to the curve for k = 1 with negative cooperativity. Describe the features of this curve in the graph above that demonstrate negative cooperativity.
C. When viewed from above the cell-surface, the representation shows receptors with one and two bound insulin molecules. Explain the negative cooperation for this receptor based on the free energy of conformational changes in the receptor-peptide chains.
D. (Can't copy)
E. Explain the advantages in terms of selection of two-site binding with negative cooperation relative to one-site binding.
F. Three binding curves with negative cooperativity and different values of k are shown on the graph. Describe conditions in which there is an advantage in having a low value of k with negative cooperativity.

Biology for AP Courses

Julianne Zedalis,…

Chapter 9, Problem 44

Instant Answer

Solved by Expert Bryan Lynn

07/26/2019

Step 1

The graph has a sigmoidal or S-shape, indicating that a small increase in concentration leads to a large change in the number of sites bound. This is because the binding of one ligand increases the affinity of the receptor for additional ligands. Show more…

Show all steps

Thanks for your feedback!

Tyrosine kinase receptors are pairs of proteins that span the plasma membrane. On the extracellular side of the membrane, one or more sites are present that bind to signaling ligands such as insulin or growth factors. On the intracellular side, the ends of peptide chains on each protein phosphorylate the other member of the pair, providing active docking sites that initiate cellular responses. The signal is switched off by dissociation of the ligand. For each ligand-receptor system, the equilibrium constant, k, controls the distribution of receptor-bound and unbound ligands. In systems with large values of k, a site is likely to be occupied, even at low concentrations of ligand. When k is small, the likelihood of binding is low, even when the concentration of ligand is high. To initiate a new stimulus response cycle for the receptor, the ligand must dissociate. Larger values of k mean that the receptor is more likely to be occupied and thus unavailable to bind another ligand. Some ligand-binding systems have multiple binding sites. For example, hemoglobin binds four oxygen molecules, whereas myoglobin has only a single binding site. When multiple binding sites are present, the presence of an already-bound ligand can cooperatively affect the binding of other ligands on the same protein. For hemoglobin, the binding is positively cooperative. The affinity of oxygen for heme increases as the number of bound oxygen molecules increases A. Describe the features in the graph above for hemoglobin that demonstrate positive cooperativity. B. The insulin receptor (IR) is a tyrosine kinase receptor that has two sites to which insulin can attach. IR is negatively cooperative. In the diagram above, the dependence of the bound fraction on available insulin is similar to the curve for k = 1 with negative cooperativity. Describe the features of this curve in the graph above that demonstrate negative cooperativity. C. When viewed from above the cell-surface, the representation shows receptors with one and two bound insulin molecules. Explain the negative cooperation for this receptor based on the free energy of conformational changes in the receptor-peptide chains. D. (Can't copy) E. Explain the advantages in terms of selection of two-site binding with negative cooperation relative to one-site binding. F. Three binding curves with negative cooperativity and different values of k are shown on the graph. Describe conditions in which there is an advantage in having a low value of k with negative cooperativity.

Play audio

Feedback

Bryan Lynn and 53 other subject Biology educators are ready to help you.

Ask a new question

Labs

Want to see this concept in action?

NEW

Explore this concept interactively to see how it behaves as you change inputs.

View Labs

Key Concepts

Negative Cooperativity

Negative cooperativity is observed when the initial binding of a ligand decreases the receptor’s affinity for additional ligands. In binding curves, this typically results in a more gradual increase in overall binding with rising ligand concentrations. Negative cooperativity can serve to moderate the cellular response to prevent overstimulation and to maintain receptor availability for new signaling events.

Functional Advantages of Multi-site Binding with Negative Cooperativity

Multi-site binding with negative cooperativity offers regulatory advantages in cellular signaling. It allows for a more graded and controlled response to ligand concentrations, preventing receptor saturation that might otherwise blunt the sensitivity to new stimuli. This tuning mechanism can improve the precision of signal transduction, allowing cells to respond dynamically to changes in their environment without overshooting the intended response.

Positive Cooperativity

Positive cooperativity occurs when the binding of the first ligand increases the affinity of the receptor for subsequent ligands. This is typically reflected in binding curves as a steep, sigmoidal response, where small increases in ligand concentration lead to large increases in binding once a threshold is reached. This mechanism is often used to ensure rapid and robust responses when a critical concentration of ligand is present.

Free Energy and Conformational Changes in Protein-Ligand Interactions

The energetics of ligand binding are deeply influenced by the free energy changes associated with conformational transitions in receptors. Binding events can induce structural changes that either stabilize or destabilize further ligand interactions. In systems exhibiting negative cooperativity, the conformational change upon initial ligand binding may increase the free energy barrier for subsequent bindings, thus reducing the overall affinity for additional ligands.

Binding Equilibrium and Equilibrium Constant (k)

The equilibrium constant in a ligand-receptor binding system quantifies the affinity between the ligand and the receptor. A high equilibrium constant indicates high affinity, meaning binding occurs readily even at low ligand concentrations, while a lower constant indicates lower affinity, requiring higher concentrations of the ligand to achieve significant binding. This concept is crucial in understanding how varying ligand concentrations can modulate signal responsiveness.

Cooperative Binding

Cooperative binding refers to situations where the binding of one ligand to a multi-site receptor influences the binding of additional ligands either by increasing (positive cooperativity) or decreasing (negative cooperativity) the receptor’s affinity for subsequent ligands. This phenomenon helps fine-tune the sensitivity and response dynamics of receptor systems to changing ligand concentrations.

Tyrosine Kinase Receptors

These are transmembrane proteins that have extracellular domains to bind ligands (such as growth factors or hormones) and intracellular domains with enzymatic kinase activity. Binding of the ligand typically triggers receptor dimerization and subsequent autophosphorylation, which serves as an initial step in signal transduction pathways that regulate various cellular functions.

Recommended Videos

Transcript

00:01 Okay, so 44 has quite a few parts, so we'll try to get through them as quickly as possible.

00:08 And part a wants us to describe the features of the graph for positive cooperativity, right? so if our x -axis is our concentration of ligands, our signaling molecules, that's the concentration.

00:23 And the y -axis is the number of sites bound.

00:29 Okay, so number of sites bound.

00:35 And positive cooperativity has this sort of sigmoidal shape, or like by sigmoidal you sort of mean like an s, s shape, right? okay.

00:51 And so what that implies here is if you take a distance, okay, like a distance on the x -axis between concentration, that's kind of short, you'll see where it connects.

01:04 On the graph here, a very different, like a large change in the number that's bound, right? and so that the ability for it to have a large change within a short, short concentration, that's what gives us this positive cooperativity.

01:25 Okay, and then part b wants us to take a look at negative cooperativity, right? and so the negative cooperativity is going to look a little bit more like this.

01:40 Okay, and so similarly, if we take a look at within our same realm here, the same gap distance that we used, you can see then that the change in the number bound for the negative cooperativity here is kind of small, right? so even though the concentration is increased, there's not much change in the number bound, whereas for our positive cooperativity, right, the number changed was quite a bit more.

02:12 Okay, so that's really the sort of major differences there and with the graph shapes.

02:25 Okay, so then we move on to part c, and this is a little bit confusing because part d, there's a typo in the textbook here, and part d gives us the images that are being described in part c.

02:37 Okay, so it gives us these sort of a bird's eye view of a receptor.

02:45 So normally we sort of like have our little cell wall and a receptor sort of is shown sticking up, but this one has two.

02:52 So instead of like a little cup, we're getting sort of two off the side, right? so it's going to look something like that.

03:01 But so we're given this image of a receptor at different stages, right? so when there's nothing in it, when it has one molecule bound, and then again, when there are two molecules bound.

03:24 Okay.

03:25 And so it's asking us to explain the negative cooperation.

03:30 So why does having more binding not have like a huge impact, right? so why is it that one being bound doesn't allow for more to be bound? and so if we kind of roll back here and think about what's happening in size.

04:00 If we have a receptor, okay, so we're going to have a receptor.

04:05 There's the extracellular part and the intracellular part, right? and once one binds, we can get our enzyme substrate...

Ace is your personal tutor. It breaks down any question with clear steps so you can learn.

Start Using Ace

Continue solving this problem

Create a free account to:

View full step-by-step solution
Ask follow-up questions with Ace AI
Save progress and study later

Please give Ace some feedback