VL 2 Flashcards
Heterotrimeric G-Proteins (35 cards)
What are G-Proteins?
G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, involved in transmitting signals from stimuli outside a cell to its interior.
What are the two classes of G proteins?
- Monomeric small GTPases
- Heterotrimeric G protein complexes
What physiological functions do G proteins influence?
- Formation of Second Messenger-Molecules (intracellular transduction. cAMP, IP3, DAG, Ca2+)
- Senses (Sight, taste, flavor, neurotransmitters)
What is the role of G-protein coupled receptors (GPCRs) in signal transduction?
GPCRs transmit extracellular signals (first messenger) to intracellular signals (second messenger)
GCPRs bestehen aus 3 Untereinheiten:
- Discriminator (resceptor), recieves Signal A
- Signal transducer (G-Protein)
- Amplifier, releases intracellular Signal to second messenger
Who were the 1994 Nobel laureates in medicine for their work related to G proteins?
- Alfred G. Gilman
- Martin Rodbell
What was the finding in the Gilman laboratory experiment with lymphoma cell lines?
cAMP wird in vielen Körperzellen gebildet, wenn ein Gs-Protein-gekoppelter Rezeptor aktiviert wird. Dabei stimuliert die α-Untereinheit des Gs-Proteins das Enzym Adenylatzyklase, das aus ATP das Signalmolekül cAMP herstellt.Die Regulation erfolgt durch G-Proteine:
* Gs-Proteine fördern die Bildung von cAMP.
* Gi-Proteine hemmen die Adenylatzyklase und reduzieren somit die cAMP-Produktion.
- Lymphoma cell line canbe induced to form cAMP by receptor X activation.
- Mutated Lymphoma cell line was unable to produce cAMP in response to receptor X activation
–> Finding 1: Receptor X normal
–> Finding 2: Amplifier (adenylyl cyclase) normal
–> Hypothesis: Tranducer molecule is missing
The normal lymphoma cell produced cAMP, while the mutated lymphoma cell was unable to produce cAMP in response to receptor activation –> Identification of first G-Protein
cAMP = zu chemischen Gruppe der Nuleotide gehörenden Signalstoff, der als second messenger in vielen Signalkaskaden von Stoffwechsel und Hormonwirkung eingschaltet wird.
What are the regulatory components of Adenylate cyclase?
Explain the circle of signal transduction: G-Protein coupled receptors (GCPRs)
Ga: Regulatory function
Gb, Gg: (normally) no regulatory function
What are the four classes of heterotrimeric G-Proteins?
- Gαs: Stimulatory on [cAMP]
- Gαi: Inhibitory on [cAMP]
- Gαq: Phospholipase C activation
- Gα12/13: Remodeling of cytoskeleton (guanine nucleotide exchange factor interaction)
What are the post-translational modifications of G-Proteins?
- Palmitoylation
- Myristylation
- Isoprenylation
What are the elements of G-protein coupled receptor systems?
- GPCR: A receptor with 7 trans-membrane helices
- A membrane-bound effector molecule (Enzyme or ion channel)
- Second messenger: Amplifies the signal
- Modulation of the signal
What are GPCRs important for?
- more than 800 G-protein coupled receptors
- They are involved in various physiological processes hence ligand that can bind to and activate GCPRs are of particular interest to pharmaceutical research.
e.g for GCPRs: Rhodopsin, Neurotransmitter receptros (Seotonin, Dopamin GABA)
What are the three classes of GPCRs?
-
Class A:
Rhodopsin/β2-adrenergic receptor type -
Class B:
Glucagon/Calcitonin-receptor type
long N-terminal domain with disulfide bonds -
Class C:
Neurotransmitter/Calcium receptor type
long N-terminal domain
What is the role of adenylyl cyclase in signal transduction?
Adenylyl cyclase
* membrane bound
* binds a-Subunit of heretodimeric G-Proteins
* Activation by Ga s / Inhibition bei Ga i
* 12 Transmembrane helices
Adenylyl cyclase converts ATP into cAMP, acting as a second messenger.
Effector protins generate second messenger
Die Adenylatzyklase ist ein membrangebundenes Enzym, das nach entsprechender Aktivierung aus ATP cAMP bildet. Damit ist die Adenylatzyklase eine wichtige Komponente bei der Signaltransduktion mit Second-messenger-Substanzen.
What does Phospholipase C do?
It hydrolyzes phosphatidyl-inositol 4,5-bisphosphate (PIP2) into inositol 1,4,5-trisphosphate (IP3) and diacyl glycerol (DAG).
Name 3 second messengers from signal transduction:
cAMP (cyclic AMP)
* Second messenger for omportant hormones: Glucagon, Insulin, Adrenalin<
* Activation of cAMP-dependent proein kinase (PKA)
–> metabolic regulation of glucose/lipid metabloism (Gluconeogenesis, Lipolysis)
DAG (diacylglycerol)
* Hydrolysis of PIP2 into DAG and PI3
* activation of protein kinase c (PKC)
–> muscle contraction, secretory processes, Vaso-/ bronchoconstriction
PI3
* soluble component
* Regulation of ca2+-Mobilization, Activation of PKC
–> Neuronal signal transduction
What are the effects of cAMP in signal transduction?
- Activates cAMP-dependent protein kinase (PKA)
- Regulates glucose/lipid metabolism
What is the function of RGS proteins?
They enhance the intrinsic GTPase-activity of G-proteins, increasing the rate of GTP hydrolysis.
What is the role of arrestins in GPCRs?
They desensitize GPCRs during long-lasting signals by phosphorylating GPCRs and facilitating internalization.
What are examples of physiological processes involving G proteins?
- Sensory perception
- Metabolic processes
- Stress/flight response
What is the mechanism of action of cholera toxin?
It locks G-proteins in a GTP-bound state, increasing intracellular cAMP levels.
What happens during the activation/inactivation cycle of G proteins in photo signal transduction?
One rhodopsin molecule absorbs one photon, activating 500 transducin molecules, leading to the activation of phosphodiesterase and hydrolysis of cGMP.
What is the function of Rhodopsin in phototransduction?
One Rhodopsin molecule absorbs one photon, activating 500 Transducin molecules
Rhodopsin is composed of Opsin and 11-cis-Retinal.
What is the result of the activation of 500 Phosphodiesterase molecules?
105 cGMP molecules are hydrolyzed
This process leads to the closure of sodium channels.
