Ligand receptor-binding Flashcards
What are the five functional classes of receptors?
Transcription factors: steroid hormones and thyroid hormones
Ion Channels: NT receptors
G protein Coupled
Enzymes: mostly growth factors
Other: a wide array
What is the general domain structure for
Transcription factors?
Ion Channels?
g-protein coupled?
Enzymes?
Transcription factors: DNA Binding Domain
Ion channels: Ion channel domain
G protein-coupled: G protein domain
Enzyme: Enzyme Domain
How does the signal could lead to different responses depending on the target?
A signal from Transcription factors, ion channels, G protein-coupled, Enzymes.
A signal that binds to Transcription factors will impact gene expression.
A signal that binds to Ion Channels will provide the basis for fat synaptic signaling in NS and skeletal muscle.
A signal that binds to G protein-coupled will cause a conformation change to a G protein.
A signal that binds to Enzymes will activate growth factor receptor
From the five receptors, functional class (Transcription factors/Ion Channels/G coupled proteins/Enzymes) is distinct due to being a hydrophobic receptor (protein)
Explain the distinct signaling pathway in this receptor functional class.
Transcription factors
They can not travel freely in the blood
Need transport carrier protein
The receptors are in the cytoplasm of the target cell, instead of the membrane (a transmembrane).
True or False:
Not all receptors have DNA binding Domains (transcription factors), Ion channel domains (ion channels), G protein-binding domain (G protein), Enzymes domains (enzymes).
Not all transcription factors, ion channels, G protein-binding proteins, and enzymes have signal binding domains.
True
What are the types of chemical bonds that mediate ligand-receptor interactions?
How the structure of the ligand and receptor determine the nature of bond formation?
(the answer is in () )
Non-covalent bonds
like
Ionic bonds (if the signal and the ligand are proteins)
Van der Walls attraction
H bonds
How is the formation of a bond between ligand and receptor can induce local conformation changes at the ligand-binding site?
Why these allosterically coupled in receptor structure are critical for signaling?
The ligand (chemistry and structure are complementary) will bind to the receptor and stabilized by the non-covalent bonds.
The receptor will induced fit, a local change in receptor structure to perform allosteric coupling, the subsequent change in local structure at a different site in the receptor resulting in output.
What is the relationship between the bonds that form between ligand and receptor and binding affinity?
If a ligand bind to a receptor that is not specific for that ligand it will form only a few weak bonds, but it will rapidly break due to thermal motional.
If a ligand bind to its specific receptor, it will form enough weak bonds to withstand thermal jolting, stay bound to each other.
What is the overall relationship between the Kd value and binding affinity?
Kd is the [L] where 50% of receptors have bound ligand
(this is in the center of the dose-response curve)
Anything below will be less than 50% and vice versa (more than 50% above).
If the curve is toward the left that means the receptor has a higher affinity toward the ligand.
if the curve is towards the right that means the receptor has a lower affinity toward the ligand.
How do you interpret saturation bind curves based on Kd and Bmax, incorporating the % of total receptor in their ligand-bound state where their ligand-bound state equals the Kd and when the ligand conc is 10X and 1000x above and below the Kd?
At the Kd
The square in purple is the effect is in tune to receive a maximum response. Here 50,000 receptors will be active with the ligand concentration.
Below the Kd
If we move 10x (one log) to the left, the number of active receptor decrease and decrease in signaling. If you move 1000x (three logs) to the left there is no active receptor so no cell response.
Above the Kd
If we move 10x(one log) to the right, the number of active receptor increase and increase in signaling. If you move 1000x (three logs) to the right all the receptors are active and the signaling plateau.
How do you interpret saturation binding curves when the Kd changes without changing Bmax, also when Bmax changes without changing Kd?
When Kd changes without changing Bmax, that means the affinity increase (moved toward the left) or decrease (moved towards the right)
When Bmax changes without Kd changes, that means the efficacy increase (move up)or decrease (move down)
Plot the saturation binding curve with COVID being the ligand.
Given: Sars-CoV-2 had a Kd of 1.5X10-10 M
Cov-2 variant has a lower Kd.
Looking at the image (not an actually represent a covid but a close sample)
The middle graph is the regular COVID binding curve.
The graph towards the left is showing the COV-2 variant, it has a higher affinity.
