Essential%20Biochemistry - PowerPoint PPT Presentation

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Essential%20Biochemistry

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... density dependant signaling Activation of Bio-film formation which affects bacterial resistance Extracellular Signals G Protein Coupled Receptors Guanyl ... – PowerPoint PPT presentation

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Title: Essential%20Biochemistry


1
Signaling via Ligand-Receptor Binding
Agonist - ligand binding to a receptor and
eliciting a response
caffeine
Antagonist - ligand binding to a receptor but not
eliciting a response
R L ? RL Kd RL/RL
2
Bacterial Quorum Sensing
Increased cell density dependant
signaling Activation of Bio-film formation which
affects bacterial resistance
3
Extracellular Signals
4
G Protein Coupled Receptors
Guanyl nucleotide binding protein Minus ligand,
a, ß, and ? subunits associated with GDP
(inactive bound form) and Plus ligand, a
subunit exchanges for GTP (active released form)
Signal propagation Activate adenylate cyclase
converts ATP to cyclic ATP Signal resetting GTP
hydrolyzed to GDP and ß, and ? subunits
re-associate
5
G-Protein Cycle and Generation of Cyclic AMP
How is adenylate cyclase activated?
6
External Signal for G-Protein Activation
ß2-adreneric receptor
7
Heterotrimeric G Protein
a, ß, and ? subunits (blue, green, and yellow,
respectively) associated with GDP (orange)
8
G-Protein Pathway Activation by Epinephrine
What is effective signaling? Specificity?
Sensitivity?
9
Adenylate Cyclase Activation/Deactivation
10
Cyclic AMP Deactivation
11
Protein Kinase A Activation by cAMP
12
Protein Kinase A Regulation by Phosphorylation
Dephosphorylation blocks substrate from active
site Catalytic subunit light green Activation
loop dark green Substrate target protein blue
13
External Signal for G-Protein Activation
a-adreneric receptor is also activated by
epinephrine and norepinephrine IP3, a product of
phosphatidylinositol bisphosphate hydrolysis
signals a calcium influx and protein kinase C
activation
14
Phosphoinositide Cascade
15
Calcium Binding Protein Calmodulin
Ca2 ions
EF-hand protein family
Extended unbound form
Bent bound to a target protein
16
Receptor Tyrosine Kinases
Operative for certain hormones and signaling
molecules that regulate growth (e.g.
insulin) Ligand binding allows the receptor
monomer to form a dimer unit with cytoplasmic
kinase domain catalytically active
17
Insulin receptor
Insulin binding site
Insulin binding site
Extracellular region
Cell surface
a,ß subunits one in space-filling (red) and
other in backbone-trace form (yellow)
18
Insulin Receptor Tyrosine Kinase Activation
Inactive form (blue) Activation loop (dark
blue) Active form (green) Activation loop (dark
green) Note Activation loop swings out with
Tyr phosphorylation
19
Ras Signal Transduction Pathway
Ras- rat sarcoma virus
Color coding red inactive green active
20
Ras Signal Transduction Pathway
21
Ras Signal Transduction Pathway
Protein phosphorylation can lead to subsequent
gene activation
22
Lipid Hormone Signaling
Includes thyroid hormones that stimulate
metabolism (right) as well as hormones for salt,
water and reproductive functions Do not bind to
cell-surface receptors Directly cross membranes
to interact with intracellular receptors
23
Lipid Hormones Eicosanoids
Regulation of blood pressure, blood coagulation,
inflammation, pain and fever Aspirin inhibits
cyclooxygenase activity and therefore serve as a
blood thinner
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