Types of receptor

2. • Ligand-gated ion channels (Inotropic receptors)
• G - Protein coupled receptor (Metabotropic receptors)
• Enzymatic receptors (Tyrosine Kinase Receptor)
• Nuclear Receptor (Transcription factors/ Steroid)

6. LIGAND GATED ION CHANNELS
• Ionotropic Receptors
• Typically receptors on which neurotransmitters act
• Timescale: Milliseconds
• Localization: Membrane
• Effector: Ion Channel
• Coupling: Direct
• Examples: Nicotinic Ach Receptor, GABAA Receptor,
Glutamate Receptor, Glycine receptor, 5 Hydroxytryptamine
type 3 (5 – HT3)

8. MOLECULAR STRUCTURE
• Nicotinic Ach receptor studied in great detail
• Pentameric Assembly of 4 types of subunits α, β, γ and δ
• 4 membrane spanning α-helices inserted into membrane
• 2 Ach binding sites, both must bind Ach molecules for receptor
activation
• Lining of central transmembrane pore formed by helical
segments of each subunit (negatively charged AA). 5 helices
sharply kinked inwards halfway, forming a constriction

12. • Metabotropic or 7 – Transmembrane/ Heptahelical receptors
• Largest family
• Timescale: Seconds
• Location: Membrane
• Effector: Channel or Enzyme
• Coupling: G- Protein
• Examples: adrenoceptors, Muscarinic Ach, histamine,
serotonin, opioid, cannabinoid, amine, peptide, prostanoid
receptors
TYPE 2 : G – PROTEIN – COUPLED RECEPTORS

13. • Single polypeptide chain 1100 residues.
• 7 Transmembrane α-helices, an extracellular N-terminal domain
and intracellular C-terminal domain
• 3rd cytoplasmic loop couples to the G- Protein
MOLECULAR STRUCTURE

14. • Family of membrane-resident proteins whose function is to
recognize activated GPCRs and pass on the message to the
effector systems that generate a cellular response
• Function of G-Protein: 3 subunits (α, β, γ) are anchored to the
membrane through attached lipid residues Coupling of the α
subunit to an agonist-occupied receptor causes bound GDP to
exchange with intracellular GTP; α–GTP complex dissociates
from receptor and from βγ complex
• Four main classes of G-protein (Gs, Gi, Go and Gq) show
selectivity with respect to both the receptors and the effectors with
which they couple
G-PROTEINS AND THEIR ROLE

23. • Location: Plasma membrane
• Function: Enzymatic activity
• Function of any Kinase enzyme: catalysis of phosphate group
transfer
• Kinase in this receptors transfers phosphate from ATP to amino
acid tyrosine.
• Inactive as monomers: Active as dimers (when phosphorylated)
• Examples: Growth factors, cytokines, insulin, etc.
Characteristics of Tyrosine kinase receptors

25. • When RTK are phosphorylated they gets activated and further
activates various proteins for cellular response.
• Two Pathways are generally followed by activation of RTKs
• A. JAK-STAT Pathway
• B. Ras-Raf MAP Kinase Pathway
• This pathways initiates gene expression and protein synthesis
Intracellular signalling after activation

26. • JAK – Janus Kinase
• STAT – Signal transducer and activator of transcription
• GRB2 protein – Growth factor receptor bound protein
• Sos protein – son of sevenless
• MAP Kinase – Mitogen activated protein kinase
• ERK – Extracellular signal regulated kinases
Important Terms

35. • Location: Cytoplasm and nuclear
• Function: Intrinsic transcription factor activity
• Structure: Simple protein structure with two ends (one with N
terminal and other with C terminal)
• DNA binding domain contains zinc finger motif, which is
specifically required to bind with DNA.
• HSP is heat shock protein and it plays important role
• Examples: Steroid receptors, Vitamin D, PPAR-gamma,
Retinoic acid receptor, etc.
Characteristics of nuclear receptors

36. Structure of Nuclear Receptors
Hinge region

37. • Two types of receptors: A. Cytoplasmic B. Nuclear
Intracellular signalling after activation
Cytoplasmic Receptors Nuclear Receptors
Homodimer required Heterodimer required
Binds DNA after activation Already bound to DNA
When inactive, bound to HSP90 and
after ligand binding, HSP90 detach
In inactive stage, bound to repressor
and detach when activated
Eg: Steroids (GC, Estrogen,
androgen), Vitamin - D
Eg: Retinoic acid, PPAR gamma,
Thyroid receptor