G protein-coupled receptors Flashcards
(21 cards)
Explain signal transduction
External signal is recieved and converted to another form to elicit a response
Extracellular signal is recieved and transported to intracellular signal B out
What happens to external signals?
Converted to internal responses
How do prokaryotic cells sense and respond to the environment?
Chemicals
How do Human cells sense and respond to the environment?
Light: Rods and Cones of the eye
Sound: Hair cells of inner ear
Chemicals in food: Nose and Tongue
What ways can cells communicate with each other?
Direct contact or chemical signals
List the general prinicples
Signals act over different ranges
Signals have different chemical natures
The same signal can induce a different response in different cells
Cells respond to sets of signals
Receptors relay signals via intracellular signaling cascades
Define signal transduction
Ability of cell to translate receptor-ligand interaction into a change in behaviors or gene expression
Explain the steps of cell signaling and response
1) Receptor ligand binding (effector enzymes)
2) Signal transduction (2’ messengers)
3) Cellular responses (target enzymes)
4) changes in the gene expression
What is the role of the G protein-coupled receptor?
Recieve signals from outside the cells and deliver them inside the cell, where the cell responds
Critical in many cell signaling pathways for development, vision, smell and taste
What are the two broad subclasses of trimeric G protein activated signal transduction pathways
Depending on their target effector enzymes:
A: Adenylyl cyclase
B: Phospholipase C
Define Rhodopsin
Rod cells in the retina contain Rhodopsin a protein with a light sensitive chemical bound
What is the structure of the G protein-coupled receptor Rhodopsin?
First structure of the family
bacterial rhodopsin
Revealed 7 transmembrane helices
Explain the process of structural changes in Rhodopsin
Light is absorbed, the cis retinal ligand is switched to trans retinal configuration
This chemical change induces a conformation change in the rhodopsin protein
Generates a signaling cascade resulting in a signal, to the brain via the optic nerve
What is the structure of Beta-2 Adrenergic Receptor?
7 transmembrane spanning helices
8th helix which runs parrallel to the intracellular face of the membrane
What process is Beta-2 Adrenergic receptor involved in?
Agonist binding -> G protein coupling and nucleotide exchange -> Activated G protein subunits regulate effector proteins -> GTP hydrolysis and inactivation of G-alpha protein
What is the structure of the G protein-coupled receptor family?
Dynamic
7 transmembrane helices
helix TM6 most mobile
Ligans/drugs stabilize one of these different states inducing a conformation change in a structure
Helices 2,5,6 and 7 of B2AR have kinks caused by?
Prolines at conserved places, which are important for activation of G protein effectors
The extracellular regions on all GPCRs dictate?
The ligand specificity of GPCRs
What does the drug beta blockers do?
Anatagnosts of Beta-2 Adrenergic Receptor (B2AR) which diminish the effects of adrenaline, slowing the heart rhythm and reducing blood pressure
What is the role of Beta-2 Adrenergic Receptor agonists?
Mimic native ligands of B2AR
Cause smooth muscle relaxation, bronchial passage dilation, vasodilation and rapid release of insulin
used to treat asthma, includes the well known Albuterol and Terbutaline
What is the role of Carazol?
Hype
Treats hypertension
Binds to the receptor binding pocket of Beta-2 adrenegic receptor, reducing the basal activity of the receptor
This interaction involves a number of amino acid residues
