G protein-coupled receptors Flashcards

1
Q

Explain signal transduction

A

External signal is recieved and converted to another form to elicit a response

Extracellular signal is recieved and transported to intracellular signal B out

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2
Q

What happens to external signals?

A

Converted to internal responses

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3
Q

How do prokaryotic cells sense and respond to the environment?

A

Chemicals

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4
Q

How do Human cells sense and respond to the environment?

A

Light: Rods and Cones of the eye
Sound: Hair cells of inner ear
Chemicals in food: Nose and Tongue

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5
Q

What ways can cells communicate with each other?

A

Direct contact or chemical signals

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6
Q

List the general prinicples

A

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

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7
Q

Define signal transduction

A

Ability of cell to translate receptor-ligand interaction into a change in behaviors or gene expression

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8
Q

Explain the steps of cell signaling and response

A

1) Receptor ligand binding (effector enzymes)
2) Signal transduction (2’ messengers)
3) Cellular responses (target enzymes)
4) changes in the gene expression

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9
Q

What is the role of the G protein-coupled receptor?

A

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

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10
Q

What are the two broad subclasses of trimeric G protein activated signal transduction pathways

A

Depending on their target effector enzymes:

A: Adenylyl cyclase
B: Phospholipase C

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11
Q

Define Rhodopsin

A

Rod cells in the retina contain Rhodopsin a protein with a light sensitive chemical bound

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12
Q

What is the structure of the G protein-coupled receptor Rhodopsin?

A

First structure of the family

bacterial rhodopsin

Revealed 7 transmembrane helices

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13
Q

Explain the process of structural changes in Rhodopsin

A

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

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14
Q

What is the structure of Beta-2 Adrenergic Receptor?

A

7 transmembrane spanning helices

8th helix which runs parrallel to the intracellular face of the membrane

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15
Q

What process is Beta-2 Adrenergic receptor involved in?

A

Agonist binding -> G protein coupling and nucleotide exchange -> Activated G protein subunits regulate effector proteins -> GTP hydrolysis and inactivation of G-alpha protein

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16
Q

What is the structure of the G protein-coupled receptor family?

A

Dynamic

7 transmembrane helices

helix TM6 most mobile

Ligans/drugs stabilize one of these different states inducing a conformation change in a structure

17
Q

Helices 2,5,6 and 7 of B2AR have kinks caused by?

A

Prolines at conserved places, which are important for activation of G protein effectors

18
Q

The extracellular regions on all GPCRs dictate?

A

The ligand specificity of GPCRs

19
Q

What does the drug beta blockers do?

A

Anatagnosts of Beta-2 Adrenergic Receptor (B2AR) which diminish the effects of adrenaline, slowing the heart rhythm and reducing blood pressure

20
Q

What is the role of Beta-2 Adrenergic Receptor agonists?

A

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

21
Q

What is the role of Carazol?

Hype

A

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