Lecture 11 Information Flashcards
What determines interactions between the ligand and receptor?
weak interactions
What are components of sensitivity?
high affinity
cooperativity
amplification of signal
Cooperativity in ligand binding receptor
refers to large changes in receptor activation with small changes in ligand concentration (allostery)
Desensitization
cells need to be able to down regulate signal transduction pathways
Receptor activation triggers a feedback inhibition circuit that shuts off the receptor or removes it from the cell surface
Integration
the cell has to look at the sum of all the different messages it is receiving and determine a response
some receptors could be sending opposing signals
List the different types of signal transduction mechanisms (for our class)
1) G-protein coupled receptors
2) Receptor tyrosine kinases
3) Receptor guanylyl cyclase
4) Internal receptors
What are the 3 components of G-protein coupled response?
Plasma membrane receptor that binds the ligand
Intracellular g-protein
Effector enzyme that gets turned on as a result of this process
What is the receptor of the GPCR pathway made of?
7 transmembrane structures, mostly alpha helices, some beta-pleated sheets
G-protein subunits
alpha, beta, and gamma subunits
usually found in the inactive form and bound to GDP
when GDP converts to GTP, the alpha subunit detaches
Epinephrine mechanism
binds to specific receptor on the cell’s surface and triggers a conformational change in the g-protein
GDP gets converted to GTP and the alpha subunit detatches
the alpha subunit activates adenylyl cyclase which catalyzes the formation of cAMP
cAMP serves as a secondary messenger to activate protein kinase A
Protein Kinase A
allosterically activated by cAMP
starts a phosphorylation cascade of enzymes that catalyze the removal of glucose from glycogen
glucose can be used in the bloodstream for energy during flight or fight response
Different types of G-protein coupled receptors
stimulatory form (Gs) inhibitory form (Gi)
Inactive form of tyrosine kinase receptor
monomers
Active form of tyrosine kinase receptor
dimerized
activated through phosphorylation cascade
Autophosphorylation
tyrosine kinases ability to phosphorylate and activate the tyrosine residues on itself
Examples of tyrosine kinase receptors
insulin and epidermal growth factor (EGF)
Receptor guanylyl cyclases
have an extracellular component that is able to bind the ligand
have an intracellular component that works directly as an enzyme and cyclizes GMP (cGMP)
NO-activated version of guanylyl cyclase
doesn’t have attachment to a transmembrane protein
important for smooth muscle relaxation because it converts GTP to cGMP
Viagra
inhibits an enzyme, phosphodiesterase, that would degrade cGMP
leads to higher levels of cGMP and an erection
Nuclear receptors
proteins in the nucleus or cytoplasm that respond to steroid hormones, retinoic acid, and thyroid hormone
alter gene expression by directly binding to DNA
Thyroid hormone
needs to use a protein channel to cross the membrane in order to reach a nuclear receptor
cannot cross the membrane on its own
How fast do nuclear receptors work?
slowly
puberty takes years for steriod hormones to work
Estrogen
needs a carrier protein to transport since it can’t dissolve in the blood
binds a cytoplasmic receptor and then the receptor goes to the inside of the nucleus where it can directly interact with DNA
Phosphodiesterase
breaks down cAMP by converting it to AMP
desensitizes the epinephrine pathway
