#GPCRs #RECGP #Receptor Effector coupling by G-Proteins

1. Receptor-Effector Coupling by G-Proteins
Name: Zarlish Attique
Roll no: 187104
BS: Bioinformatics
Semester: 5th
Subject: Pharmacoinformatics
Teacher: Muhammad Imran Sharif
Date: 21,December,2020
Government Post Graduate College Mandian Abbottabad
Power point slides created by Zarlish Attique

2. G-Proteins(guanine nucleotide-binding proteins)
1. G proteins are membrane resident a family of proteins that are involved
in transmitting signals from a variety of stimuli outside a cell to its
interior.
2. Their activity is regulated by factors that control their ability to bind to
and hydrolyze guanosine triphosphate (GTP) to guanosine
diphosphate (GDP).
3. Two classes of G proteins: The first function as monomeric small
GTPases, while the second function as heterotrimeric G
protein complexes. The latter class of complexes made up
of alpha (α), beta (β) and gamma (γ) subunits.
4. Types of G-Proteins: Gs, Gi, Go, Gq.
Figure: Cartoon structure of G-
Proteins 2
Topic: Receptor Effector Coupling by G-Protein

3. G-Protein coupling receptors (GPCRs)
1. Seven Transmembrane Domains (TMDs) 3 intracellular loops, 3
extracellular loops, N- and C-teminals.
2. Only found in eukaryotes including yeast, choanoflagellates, and
animals.
3. The ligands that bind and activate these receptors include light-
sensitive compounds, odors, pheromones, hormones,
and neurotransmitters, and vary in size from small molecules
to peptides to large proteins.
4. Largest class of membrane receptor and are also the most common
target of therapeutic drugs.
5. They are unique Membrane proteins, single polypeptide.
6. Ligands can’t directly move to inside the cell.
7. Type 2 couple receptors of receptors family.
8. The 2012 Nobel Prize in Chemistry to Brian Kobilka and Robert
Lefkowitz for their work on GPCR function.
Figure: Structure of GPCRs: Seven
transmembrane helices with terminals
Topic: Receptor Effector Coupling by G-Protein 3

4. Receptor Effector coupling by g-protein, Mechanism of Action
1. Ligand bind to the GPCRs and undergoes
conformational changes.
2. Alpha-unit exchanges GDP to GTP.
3. Alpha-unit dissociates and binds to the
effectors (enzymes, or other proteins).
4. Beta-gamma dimer binds to ion channels
and kinases.
5. Target protein on alpha-unit rely signals
via second messenger.
6. Things go to normal.
Topic: Receptor Effector Coupling by G-Protein 4

5. Step By Step: Receptor Effector Coupling by g-protein with example of adenyl cyclase
Topic: Receptor Effector Coupling by G-Protein
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6. G-Proteins and Effectors
Effectors form a diverse group of proteins through their interaction with G-proteins that act either as
secondary messengers or lead directly to a cellular and physiological response. Many proteins such as
tubulins, adenylate cyclases, ion channels and others act as effectors.
Topic: Receptor Effector Coupling by G-Protein 6

7. References
• https://pubmed.ncbi.nlm.nih.gov/2160274/
• https://doi.org/10.1210/edrv-13-3-536
• https://dx.doi.org/10.1093%2Fdatabase%2Fbaq019
• https://www.ncbi.nlm.nih.gov/books/NBK21718/
• https://www.sciencedirect.com/science/article/pii/03044157909000
7Y
• Questions Answer session!
Topic: Receptor Effector Coupling by G-Protein
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