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    Unacademy 2 PDF

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    ANUPAM ANAND KUMAR PANDEY MBA-I
    The document discusses thyroid hormone receptors and their interactions with DNA and other proteins. Specifically: - Thyroid hormone receptors are located in the nucleus bound to DNA even without their ligand. - The hormone response element has two half sites that thyroid receptors bind to, forming a heterodimer with retinoid X receptors. - When ligands bind to the receptors, corepressors are removed and coactivators are recruited, allowing gene transcription.

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    Unacademy 2 PDF

    Uploaded by

    ANUPAM ANAND KUMAR PANDEY MBA-I
    20 views26 pages
    The document discusses thyroid hormone receptors and their interactions with DNA and other proteins. Specifically: - Thyroid hormone receptors are located in the nucleus bound to DNA even without their ligand. - The hormone response element has two half sites that thyroid receptors bind to, forming a heterodimer with retinoid X receptors. - When ligands bind to the receptors, corepressors are removed and coactivators are recruited, allowing gene transcription.

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    The document discusses thyroid hormone receptors and their interactions with DNA and other proteins. Specifically: - Thyroid hormone receptors are located in the nucleus bound to DNA even without their ligand. - The hormone response element has two half sites that thyroid receptors bind to, forming a heterodimer with retinoid X receptors. - When ligands bind to the receptors, corepressors are removed and coactivators are recruited, allowing gene transcription.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    20 views26 pages

    Unacademy 2 PDF

    Uploaded by

    ANUPAM ANAND KUMAR PANDEY MBA-I
    The document discusses thyroid hormone receptors and their interactions with DNA and other proteins. Specifically: - Thyroid hormone receptors are located in the nucleus bound to DNA even without their ligand. - The hormone response element has two half sites that thyroid receptors bind to, forming a heterodimer with retinoid X receptors. - When ligands bind to the receptors, corepressors are removed and coactivators are recruited, allowing gene transcription.

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    © All Rights Reserved
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    of 26

    Thyroid Hormone Receptors…….

    • These receptors are located inside the nucleus bound to DNA even in
    the absence of the ligand .
    • The HRE has two half sites, but here TR binds to only one of the half
    sites and the other binds retinoid X receptors (RXR).
    • So, when both binds to the two DNA half-sites of the response
    element, forming a heterodimer.
    • HRE is inhibited due to a corepressor bind to TR that inhibit gene
    transcription. When a ligand binds to it corepressor is removed and
    coactivator are recruited
    Cell Surface Receptors
    Hydrophilic molecules and some lipophilic molecules (eicosanoids).
    Topics for today
     Nuclear Receptors.
     GPCR and G-Protein
     Classes of trimeric G-Protein
     Cyclic AMP and Protein Kinase A
     Gq and Phospholipase-Cβ
     Cholera Toxin
     Pertussis Toxin
    Classes
    G-Protein Ion-Channel
    Coupled Receptors
    Receptors (GPCR)

    Enzyme linked
    receptors
    GPCR and G-Protein
    • They are cell surface receptors that transmit signal to intracellular
    target via guanine nucleotide binding protein called G-Protein.
    • Ligands- neurotransmitters, neuropeptides and peptide hormones.
    • GPCR has single polypeptide of multipass nature crossing 7 times the
    lipid bilayer. It is called serpentine receptors also.
    • Receptor for epinephrine is known as β-adrenergic receptors.
    • G-Protein-GTPase switch protein. Trimeric G-Protein Monomeric G-Protein
    ON-GTP OFF-GDP
    MONOMERIC G-PROTEIN
    • RAS-Regulates cell growth
    • RHO-reorganize cytoskeleton
    • RAB-Vesicle Targeting and Fusion
    • RAN-transport in and out of Nucleus
    • SAR-Vesicle formation
    • ARF-Vesicle formation
    • G-protein is bind to the cytoplasmic face of plasma membrane.
    • Here, it is trimeric with subunits α, β, γ. The α and γ are anchored to
    lipid membrane and Gβ is complexed with γ (heterodimeric).
    • GTP binds to Gα as Gα is GTPase switch protein.
    • So dissociation of Gα-GTP from Gβγ complex interacts with effector
    protein leading to changes.
    • Intrinsic Gα hydrolyse again GTP GDP and associate again with
    Gβγ.
    Classes of trimeric G-protein
    Members Action Function
    Gαs (stimulatory) Alpha Activate adenylyl cyclase
    Gαolf (olfactory) Αlpha Activate adenylyl cyclase
    Gαi Alpha Inhibits adenyl cyclase
    Gαgust Αlpha Activate
    phosphodiesterase
    Gq Alpha Activate phospholipase C-β
    Gαt (transducing) Αlpha Activates c GMP
    phosphodiesterase
    Cyclic AMP and Protein Kinase A
    • cAMP activates cAMP dependent protein kinase termed protein kinase A (PKA)
    • PKA catalyses the transfer of terminal phosphate group from ATP to Serine and
    threonine.
    • PKA Regulatory subunits

    Catalytic subunit

    • When both are binded- INACTIVATE


    • When dissociate left only with catalytic subunit- ACTIVATE
    • This can activate CREB (cAMP response element binding protein) by
    phosphorylation now can stimulate gene expression.
    phoshothreonine
    Property Adrenaline Estrogen
    SOLUBILITY Water-Soluble Lipid Soluble
    RECEPTOR Membrane bound Cytosolic
    PRIMARY EFFECT Enzyme Activation Gene Expression
    DURATION OF EFFECT SHORT LONG
    Gq and Phospholipase C-β
    • Gq activates the plasma membrane bound enzyme phospholipase C-β.
    • Requires presence of Ca+². Four classes of PLCs-PLCβ,-γ,-ε.

    PHOSPHATIDYLINOSITOL Inositol 1,4,5-


    4,5-bisphophate (PIP₂) triphosphate (IP₃)

    diacylglycerol
    • IP3 is a small polar molecule released into cytosol and signal signal the release of
    Ca²+ ions by binding ligand gated ca+2 ions channel on endoplasmic reticulum.
    • DAG with Ca²+ ions activates Protein Kinase C (PKC)
    • Increased Ca²+also bind calmodulin (cytosolic acidic protein) in a cooperative
    manner.
    • Calmodulin acts both directly through interaction with key target enzymes , and
    indirectly, via specific kinases (CAM Kinase). CAM Kinase also phosphorylate gene
    regulatory protein eg CAM kinase II found in nervous tissue.

    Biosynthetic
    Cell motility exocytosis
    metabolism

    Cytoskeletal Modulation of
    assembly calcium conc.
    CHOLERA TOXIN Pentameric
    protein binds
    A subunit that ADP-ribosylates to the
    ganglioside
    G-Protein.
    GM1 on the
    surface of
    intestinal
    A subunit ribosilate the Arg residue of
    epithelium
    α-subunit of Gs protein. ADP Ribose is
    provided by NAD+.

    A subunit will be altered and cannot hydrolise its


    bound GTP.

    Activation of PKA which phosphorylate CFTR and Na-H


    exchanger .
    Pertussis Toxin
    • Cholera toxin-Enterotoxin
    • Pertussis toxin- EXOTOXIN
    Causes whooping cough secreted by Bordetella pertussis
    • ADP ribosylation of Cys residue of a α-subunit of Gi.
    • Adenyl Cyclase is activated.
    QUESTIONS
    • The second messenger that opens calcium ions pores in the
    endoplasmic reticulum and plasma Membrane is
    1. Diacylglycerol
    2. Phosphatidyl Inositol biphosphate
    3. cAMP
    4. Inositol triphosphate
    • Pertussis toxin acts on-
    1. GPCR
    2. α-subunit of G-protein
    3. Βγ-subunit of G-protein
    4. Cyclic AMP

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