GPCR Flashcards
revision
1
Q
GPCR Receptor properties?
A
N-terminal: Extracellular
C-Terminal: Cytosolic
Integral membrane protein
Heptahelical-sepentine
2
Q
G-Protein
A
300 amino acids
3
Q
Membrane bound enzyme
A
Adenylyl cyclase
4
Q
G protein
A
anchoring to memb.: Through palmitoyl group
Hetrotrimeric : α, β, γ
5
Q
Gα
A
Largest
45 KDa
Linked Through palmitoyl group
Have GTPase action
Expose Guanine ntd. Binding site
6
Q
Gα + GDP
A
Inactive
High affinity for β, γ
7
Q
Gα + GTP
A
Becomes active
Affinity for β, γ decreases
8
Q
Gβ
A
Intermediate
37 KDa
9
Q
Gγ
A
smallest
9 Kda
lipd anchoring
10
Q
signal transduction molecule in GPCR?
A
Adenylyl cyclase
11
Q
secondary messengers.
A
cAMP
12
Q
PKA
A
2 regulatory Subunit (2R) R2
2 Catalytic Subunit (2C) C2
1 AKAP
13
Q
1 Regulatory unite has ____ Binding site for cAMP.
A
1
14
Q
what happen once 1 cAMP binds with 1 regulatory subunit?
A
Another Binding site for cAMP get exposed on same Regulatory subunit.
15
Q
How many cAMP is required to bind with 1 Regulatory subunit?
A
2
16
Q
Catalytic subunit has?
A
Kinase activity
17
Q
Catalytic subunit phosphorylate the?
A
CREB
cAMP Response element Binding
18
Q
CREB Binds to?
A
CREB Binding Protein (CBP)
19
Q
CREB Binding Protein (CBP) act as a?
A
Transcription Factor
20
Q
In case of adenylyl cyclase, we get?
A
PKC
21
Q
In case of Guanylyl cyclase, we get?
A
PKG
22
Q
In case of PLC, we get?
A
we get PIP2: IP3 and DAG
23
Q
Gq?
A
Gα that activates PLC
24
Q
PLC has ____ isoforms.
A
6
25
Name 6 isoforms of PLC.
Beta
gamma
Delta
Epsilon
Omega
Tou
26
All isoforms has same function, i.e?
Hydrolysis of PIP2
27
DAG is
Memb. bound because glycerol is hydrophobic.
28
Inositol is
Sugar and hydrophilic in nature, that's why found in cytosol.
29
IP3 Receptors present on?
SER membrane
29
All secondary messenger in GPCR?
cAMP
cGMP
IP3
DAG
Ca^2+
30
IP3 receptor is
Ligand Gated Ion channel
passive
along the gradient
Downhill
Ion transport
Gated- barrier
Increases the calcium concentration in cell
31
DAG provide function through?
PKC
32
PKC has ____ domain?
2
33
2 Domains of PKC binds with?
1 domain binds with DAG
2nd domain binds with Ca ion
34
Ca ion as secondar messenger?
Comes outside of the cell
G-protien directly opens the ca ion channel
35
Ligands of GPCR
calcitonin
PTH
Glucagon
Smatostanin
TRH - TSH
ADH
CRH-ACTH
GnRH- LH, FSH
GHRH-GIH
Oxytocin
Epinephrin
Nor-epinephrine
36
Neurotransmitter for GPCR
Dopamine
Serotonin
Glycine
Acetylcholine
GABA
37
Immunomodulatory for GPCR- all binds to GPCR
Histamine
Bradykinin
38
Sense- all binds to GPCR
Gustatory
Olfactory
Vision
39
Other Hormone
hCG
Angiotensin II
40
Ligands for cAMP
Calcitonin
PTH
Glucagon
Epinephrine
Nor-Epinephrine
LH, FSH, TSH
ACTH
CRH
hCG
Histamine
41
Ligands for IP3
GnRH
Oxytocin
Angiotensin II
42
Ligands for cGMP
Nitric Oxide
Carbon monooxide
ANP (Atrial Natreuretic Peptide)
43
G-protein helps in?
cell proliferation
Vesicle movement
Trafficking
RAB
Export and import from the nucleus
RAN
Translation (EF2)
44
RAB Proteins
RAB proteins are a family of small GTPases that play key roles in the regulation of vesicle transport within cells. They help in determining the specific destination of vesicles and are crucial for processes like membrane trafficking, organelle movement, and exocytosis.
45
RAN Proteins
RAN is another small GTPase involved in the transport of proteins and RNA across the nuclear envelope. It regulates the import of proteins into the nucleus and the export of RNA and ribosomal subunits out of the nucleus, playing a critical role in maintaining cellular function and gene expression.
46
RAB and RAN proteins?
Both RAB and RAN are vital for cellular communication and function, facilitating the movement of materials within and between cellular compartments.
47
2 photoreceptor?
Rods
Cones
48
Cones Types?
Blue
Green
Red
49
Rhodopsin?
IMP
Present in Rod cells
light absorbing pigment
50
secondary messenger for Rhodopsin?
cGMP
50
Glucagon on GPCR. Happens in?
in Livers cells
51
cAMP acts on (Phosphorylates)?
1. Phosphorylase Kinase
2. F6P2 kinase
3. Glycogen synthase
4. PDE
52
Role of Phosphorylase Kinase?
Glycogenolysis: Breakdown of Glycogen into Glucose
53
Role of F6P2 kinase?
Gluconeogenesis: Synthesis of Glucose from Non carbohydrate source
54
Role of Glycogen synthase?
Inactivate the synthesis of Glycogen
54
Glucagon binds to GPCR when
Glucose level is low in Blood.
55
Termination of Pathway by Ligand?
Concentration of Ligand
Presence or Absence of Ligand
56
Termination of Pathway by GTPase?
GTPase hydrolyses the GTP into GDP. Once GTP is hydrolyzed, the G-protein reverts to its inactive state (GDP-bound), causing it to dissociate from the effector proteins and the GPCR.
57
Desensitization?
Desensitization is a process by which a cell becomes less responsive to a stimulus after prolonged exposure to a signaling molecule, such as a hormone or neurotransmitter.
57
RGS proteins?
RGS proteins accelerates process of Hydrolysis of GTP by GTPase.
58
Desensitization in GPCR occurs through several mechanisms:
1. Receptor Phosphorylation
2. Receptor Phosphorylation
3. Receptor Internalization
59
Who phosphorylates beta-ARK?
PKA
59
Receptor Internalization?
Desensitized receptors may be internalized into the cell, further decreasing their availability and responsiveness to the ligand.
59
Receptor Phosphorylation?
After receptor activation, specific kinases (like GRKs) phosphorylate the receptor, which reduces its ability to activate G-proteins.
59
Arrestin Binding?
Phosphorylated receptors can bind to arrestin proteins, preventing further G-protein activation and often leading to receptor internalization (removal from the cell surface).
59
role of beta-ARK in desensitisation?
beta-ARK phosphorylates the activated GPCR at specific serine and threonine residues. This modification reduces the receptor's ability to interact with and activate G-proteins.
60
beta-ARK is recruited by?
G-βγ subunits
61
beta-ARK phosphorylates the receptor at ?
specific serine and threonine residues at C-terminal.
62
what binds at phosphorylated serine and threonine residues?
Cytosolic Beta-Arr-2 (Beta-arrestin)
63
Disease Bcz of GPCR?
Cardiovascular disorders
Blindness
Cholera
Pertussis
64
Toxin in Cholera?
AB Type
65
AB5
A is 1 in no.
B is 5 in no.
66
A is
enzymatic
ADP Ribosyl transferase: ADP ribosylation
67
Toxins reach to?
RER.
68
B is
Non enzymatic
helps toxins to enter in host.
B allow to select the host cell
69
In RER ____
A and B gets separated.
A is cleaved into A1 and A2
70
A2 is _____
enzymatic
71
A2 perform?
ADP Ribosylation
72
action of ADP Ribosylation on G-alpha in case of cholera (GPCR)
Cholera toxin transfers an ADP ribose group to a specific amino acid (typically an arginine) on the G-alpha subunit of Gs, preventing it from hydrolyzing GTP to GDP.
73
Constitutive Activation
This modification locks the G-alpha subunit in its active GTP-bound state, causing continuous stimulation of adenylate cyclase.
74
Effect of prolonged activation of protein kinase A, in intestinal cells?
In intestinal cells, this results in excessive secretion of chloride ions and water into the intestinal lumen, causing severe diarrhea, a hallmark symptom of cholera.
74
Effect of Constitutive Activation?
cAMP level Increases
prolonged activation of protein kinase A
75
Effect of prolonged activation of protein kinase A?
Acts on CFTR
Disrupts normal cellular functions.
76
CFTR?
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a protein that functions as a chloride channel in epithelial cells, playing a crucial role in maintaining the balance of salt and water across cell membranes.
77
Receptor for Cholera Toxin?
GM1
78
GPCR in Diptheria?
Caused by "Corny Bacterium"
79
Role of GM1?
The binding of cholera toxin to GM1 triggers endocytosis, allowing the toxin to enter the cell where it can exert its effects.
80
Nature of Toxin?
AB Type
81
AB Type does
ADP Ribosylation at His-Residues of Elongation Factor-2.
82
Pertussis caused by ?
ADP ribosylation of G-protein at 16 a.a of Respiratory cells.
Results in no exchange of GDP to GTP. G-protein remains Inactive
82
GPCR in Pertussis?
Caused by "Bordetella Pertussis"
Gram negative
Infect Respiratory Tract
83
The Walker motif plays a critical role in ?
this nucleotide exchange process, enabling the G-protein to transmit the signal downstream.
83
which residues in the toxin are crucial for ADP Ribosylation in Pertussis?
Cysteine
83
The cysteine residues are involved in ?
The cysteine residues are involved in the structural integrity and function of the toxin, allowing it to effectively enter host cells and disrupt normal GPCR signaling by inhibiting Gi protein activity.
83
Walker motif's sequence with a consensus pattern ?
GXXXXGKS/T
83
Stimulatory G-Protein (Gs)?
When GHRH binds to its receptor on somatotrophs, Gs is activated, stimulating adenylate cyclase to increase cAMP levels. This cascade enhances GH synthesis and secretion.
83
Walker motif?
It refers to a specific sequence of amino acids found in G-proteins and some other ATP-binding proteins, crucial for their function. Walker motif is involved in the binding of guanine nucleotides (GTP and GDP).
84
GPCR in somatotroph?
somatotrophs are regulated by the opposing actions of GHRH and somatostatin, which interact with GPCRs linked to stimulatory and inhibitory G-proteins, respectively.
84
Guanine interact with only?
K,S/T by Hydrogen Bond
84
Walker motif is essential for?
GTP binding
84
Inhibitory G-Protein (Gi)?
When somatostatin binds to its receptor, Gi is activated, inhibiting adenylate cyclase and reducing cAMP levels. This inhibition decreases GH release.
