Physiology 3140A Lecture Notes - Lecture 16: Dna-Binding Domain, Nuclear Receptor, Membrane Transport Protein
2 May 2018
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Cell Physiology Lecture 16
Major Receptor Classes
October 23 2017
Extracellular Signal Molecules Bind to Specific Receptors
- Two types of receptors:
o Cell surface receptors
o Intracellular receptors
- Target cell responds by means of a receptor protein which specifically binds the signal molecule, then
initiates a response
Intracellular Receptors
- Ligand molecule is outside of the cell
o Tend to be small, hydrophobic molecules
- Some signal molecules [ligands] diffuse across membranes and bind to receptors in either cytosol or
nucleus
o Ligands are hydrophobic, small
▪ E.g. Hormones
▪ Since they are hydrophobic, they are NOT good at floating in the blood stream; have
to be bound to a protein carrier to be soluble and transported in aqueous
environments
- Ligand can passively diffuse across the plasma membrane (hydrophobic); released from carrier
protein (if bound to one) and passively diffuse into cells
- Once it gets into the cell it can either:
o Bind to another carrier protein inside the cell (aqueous environment) and help them across
the nuclear envelope into the nucleus where they bind a receptor
o OR the intracellular receptor may be in the cytoplasm and they can bind to the intracellular
receptor right there
- After ligand binding, receptors translocate to the nucleus
o Many diverse ligands, but have similar mechanism of action – regulate gene transcription
- Goal: regulate gene transcription
o Not much signaling involved
find more resources at oneclass.com
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The nuclear receptor superfamily
- Common features of nuclear receptors:
o Have DNA binding domain
▪ Differ for different receptors because they have to find different parts of DNA to
bind to
▪ Consensus sequence they have to bind on DNA is different because regulate the
transcription of different genes
▪ Configuration of the DNA binding domain and what it recognizes differs
o Carboxyl and amino ends
o Transcription activating domain
o Ligand binding site
▪ The ligand binding site is unoccupied. There is an inhibitor protein associated that
when the ligand is not bound, the inhibitor protein will prevent the nuclear receptor
from binding the DNA, often (not 100%, but it is the norm)
• INACTIVE RECEPTOR
▪ Receptor will not anchor with the inhibitor protein and the conformation the
protein is in
o Inhibitory protein
- Now the ligand can bind to it, and causes a conformational rearrangement
o Co-activator protein may bind or not
o Change in the shape of the protein get binding to the appropriate binding site of DNA
activate gene transcription
- Do not always get activation of gene transcription, can get repression of gene transcription
- Ligand receptor process is not always activation; can get repression
o Just a change in gene transcription is the important idea!
find more resources at oneclass.com
find more resources at oneclass.com
The nuclear receptor signaling
- Cortisol bound to carrier molecule
- Ligand passively diffusing across the plasma membrane, coming into the cytoplasm
- Nuclear receptor is in the cytoplasm
o Recognizes the ligand
- Get a conformational change in the configuration of the protein
- Changes it into an activated receptor that translocate into the nucleus, and alters DNA transcription
Cell Surface Receptors
- 3 large super-families of cell surface receptors:
o 1) Ligand-gated ion channel receptors
o 2) G-protein-coupled receptors
o 3) Enzyme-linked receptors
- Hydrophilic ligands;
o Can not passively diffuse across the plasma membrane
o For it to impact the behavior of the cell, it has to be recognized at the cell surface
o E.g. neurotransmitters
- If there is no receptor at the cell surface, nothing will happen!
o The ligand can not diffuse into the cell through the plasma membrane
- The cell surface receptor recognizes the ligand + signaling takes place
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Two types of receptors: cell surface receptors. Target cell responds by means of a receptor protein which specifically binds the signal molecule, then initiates a response. Ligand molecule is outside of the cell: tend to be small, hydrophobic molecules. Some signal molecules [ligands] diffuse across membranes and bind to receptors in either cytosol or nucleus: ligands are hydrophobic, small, e. g. Since they are hydrophobic, they are not good at floating in the blood stream; have to be bound to a protein carrier to be soluble and transported in aqueous environments. Ligand can passively diffuse across the plasma membrane (hydrophobic); released from carrier protein (if bound to one) and passively diffuse into cells. After ligand binding, receptors translocate to the nucleus. Many diverse ligands, but have similar mechanism of action regulate gene transcription. Goal: regulate gene transcription: not much signaling involved.
