TBL-7 Protein Modification and a Signaling Introduction Flashcards
Glycosylation and example
which one is our focus here
attach a sugar to an N or O of peptide
ex:
(1) Asparagine-linked (N-linked), covered later
(2) Serine/threonine-linked (O-linked) , covered later
(3) GPI Anchors
example of pathogen that uses glycans to gain cell entry
RBD (covid 19) recognizes N322 glycan on ACE2 (receptor) in lung
Innate immune system response
Innate immune system
distinguishes self from non-
self through the activity of pattern recognition receptors.
these immune cells have glycan-type toll-like receptors TLC-4 that recognize lipopolysaccharides found on the surface of
gram-negative bacteria and not in humans
induces inflammatory response proteins, phagocytosis
glycan-type receptor in innate immune system
TLC 4
Phagocytotic Leukocytes of Innate Immune system
name the 3
Neutrophils: In the bloodstream, detect infection with pattern recognition receptor, destroy small pathogens
Eosinophil-similar but target larger pathogens
Macrophages- differentiate from monocyte. Major function: Destroy human cells that have been compromised
innate immune cells initiate signaling increasing expression of many target genes by signaling pathways ________ and ______
G-protein coupled receptors like GPI modifications and JAK/SAT
what are the expressed proteins after the innate system has been triggered
(A) Chemokines- glycoproteins that attract other white cells (positive
feedback). The initiate signaling in target cells
(B) Complement pathways- is activated in three different manners at the
local infected site. Leads to recruitment of white cells, enhanced
phagocytosis by the process of opsonization and pathogen cell
membrane lysis.
(C) Adhesion molecules – many but forms a barrier and helps make cells
stick to the infection site.
chemokines
Chemokines-glycoproteins that attract other white cells (positive
feedback). The initiate signaling in target cells
Complement pathways-
Complement pathways- is activated in three different manners at the
local infected site. Leads to recruitment of white cells, enhanced
phagocytosis by the process of opsonization and pathogen cell
membrane lysis.
Adhesion molecules
Adhesion molecules – many but forms a barrier and helps make cells
stick to the infection site.
neutrophils burst open to form barrier
what an example of response with GPI anchors being cleaved in alpha Q
histamine release which bind to the H1 receptor
adaptive immune system
and cells
slow response
adaptive immune system termed lymphocytes and derive from
the “common lymphoid progenitor.” Two main types
(A) B-cell: produce antibodies and present pathogenic material to t-cells
(B) T-cell: directly kill infectious cells, activate other immune cells, regulate
immune response through cytokines.
what are GPI on GPCR and how does it work
in GPCR-aplha Q
they are glycolipids within the GPCR that anchor it to the cell membrame and if it get cleaved then initiates response
the glycolipids are localized within the cholesterol and sphingolipids
released from phospholipase C
H1 receptor drugs and their brand names (5)
and how do they work
second generation:
They bind to the H1 receptor but have a charge so they do not cross the barrier and do not make you sleepy
cetirizine (antihistamine) =trade name (zrytec)
levocetirizine= xyral
loratadine =claritin
desloratadine=clarinex
fexofenadine=allegra
hydroxylation
hydroxyl group to Proline and several
other amino acids
hydroxylation stabilizes collagen’s triple helical structure at every 3rd AA
lack of Lack of Vitamin C leads to ___
Scurvy: defective collagen formation leading to
subcutaneous hemorrhage, aching bones, joints,
and muscle in adults, rigid position and pain in
infants
Recommended daily amount: 75 mg (W), 90 mg
(M)
how does vitamin C help in the hydroxylation of collage
Collagen hydroxylation by prolyl-hydroxylase using
Vitamin C as a cofactor
Lipidation and examples
or attachment of a lipid to a protein can be
used to anchor proteins to membranes
(1)Sequesteration of proteins to membranes
(2) S-palmitoylation
what happens during S-palmitoylation
attaches a C16 palmitoyl group to the thiol of cysteine aa to give the protein a permanent ancher
but could be cleaved by thioesterases, therrefore can be used an an ON OFF switch for
what happens to old proteins that are S-pamitoylated
acyl protein thioesterase can break the link of the cys and anchor and can be degraded in proteosome
how does the ubiquitin proteosome system work?
the protein becomes inactivated when ubiquitin get attached to it.
ligases attach to ubiquitin ising isopeptide bond
then it is recognized by 26S proteosome —> degradation of protein and recycling of ubiquitin
what happens with ubiquination under too much stress
more proteins being degraded and leads to cell death
protein folding disorders
alzeheimers and huntigntons are diaseases due to not enough protein being degraded
biologiocal signaling metabolic view
Outside information altering energy currency (ATP) usage and allocations in
a specific way.
Needs:
A) Specific for given situation
B) Amplifies (ie more ATP)
C) Integrates: on and off
D) timely: local and shuts off
types of signaling
autocrine , immune ceels
signaling across cell junctions , neurons
paracrine , growth factors locally synchronize tissue
endocrine , hormones
GPCR alpha S system (cAMP)- cAMP
endrocrine hormones
FLAT ChAMP CHuGG
FSH, LH, ACTH, TSH (FLAT)
CRH, hCG, ADH v2 receptor, MSH, PTH, (CHAMP)
calcitonin, histamine (h 2 receptor), Glucagon and GHRH(growth hormone releasing hormone) (CHuGG)
GPCR alpha alpha Q system ( IP3)
GOAT HAG
GnRH, Oxytocyn, ADH v1, TRH (GOAT)
histamine (H1 receptor), Angiotensin II, gastrin (HAG)
GPCR mechanism description until alpha subunit
in resting state, phosphate bound to protein
3- Gprotein subunits alpha beta and gamma with GDP bound
induced state:
ligand binds, phosphates come off, GTP displaces GDP
alpha unit disassociates ( follow S or Q system)
the alpha S subunit of GPCR activate_____ and the ligand are_____ and ________
adenyl cyclase
Glucagon
epinephrine to regulate metabolic enzymes
the alpha Q subunit of GPCR activates_____ and the ligands are _____ and ________
phospholipase Cβ
epinephrine (fear)
acetylcholine
alpha i inhibits ____ and the ligands are____ and ____
adenylyl cyclase
serotonin(CB1) and cannabis(CB2)
brings you to relax state
Mechanism after release of GαS
in resting state, phosphate bound to protein
3- Gprotein subunits alpha beta and gamma with GDP bound
induced state:
ligand binds, phosphates come off, GTP displaces GDP
alpha unit disassociates ( follow S
release of Gαs activates adenylyl cyclase (AC) —>cAMP —->many PKA —->target protein are phosporalated
Mechanism after release of Gα Q
what are the 2 pathways
in resting state, phosphate bound to protein
3- Gprotein subunits alpha beta and gamma with GDP bound
induced state:
ligand binds, phosphates come off, GTP displaces GDP
alpha unit disassociates ( follow Q
- aplha Q binds to phospholipase C and PIP 2(cleaved into IP3 and DAG)
—>IP3 + DAG —> PKC —–> target protein Phos - aplha Q binds to phospholipase C and PIP 2
—>IP3—>Ca 2+ release —-> calmodulin carries Ca2+
—> ACTIVATES CaM kinases —>target protein
how does Cholera infection occur
and how does cholera enter the body
and what Alpha system does it activate
caused by Vibrio cholerae
Voluminous rice water diarrhea
-Contaminated drinking water or aquatic species in same water
- Two major virulence factors:
(1) cholera toxin and (2) toxin-coregulated pilus
- Gram-negative bacteria that use flagella to bypass mucosal lining (intestines)
- Toxin-coregulated pilus binds to
membrane ganglioside in
intestines - Cholera toxin frees Alpha protein
leading to activate adenylyl
cyclase - Target proteins that activates:
CFTR: Cl- and H2O transported out
(back to intestine) - Rice water diarrhea
Wooping cough infection
virulance factors
vaccine against it
and what G system does it affect
Bordetella pertussis —> Pertussis toxin
-Airborne bacteria that infects the airways by breathing in
droplets
-Coughing and similar symptoms (whooping) symptoms
-Largely eliminated (DTaP) immunization for infants
- Two major virulence factors: (1) pertussis toxin (PTX) binds to cell receptor (2)adenylate cyclase toxin
- Pertussis toxin activates adenylyl cyclase by “inhibiting the
inhibitor” thus increasing cAMP
how are the GPCR signals terminated
Phosphodiesterase –> cAMP to AMP
Phosphorylation: GPCR is forced to inactive state
beta Arrestin binds to receptor in place of trimeric G protein
lipid hormones signaling
examples
intracellular receptors, cross cell membranes change transcription, translation and metabolism.
CAT PET TV
Cortisol, Aldosterone, testosterone
Progesterone, estrohen, T3 , T4, Vit D
classes of steroid hormones
glucocorticoids (C21) –
deal with stress by increasing gluconeogenesis and down regulating immune action
mineralcorticoids (C21) –
maintain water and salt balance
progestogens (C21) – Sex hormone involved in menstrual cycle and reproduction
androgens (C19) – male sex hormones
Estrogens (C18) – female sex hormone
GAMPE
Biochemistry of glucocorticoids
from adrenal cortex
Mechanism: dimerize and bind promoter to regulate genes as
enhancer (increase expression) or down (repression)
cortisol
what are the effects of cortisol
increase activity of CNS, liver adipose, heart/pancrease
by increasing act of appetite, blood pressure, insulin resistance (cells dont take much gluc, sucked in by liver)
gluconeogesis
it also decreases activity of skletal muscle, fibroblast (Fb) immune system and bone
by deacreasing wound healing (fB), inflammation, bone formtion, muscle prefer protein
dexamethdone
type of glucocorticoid
change mRNA in tissues
decreases inflammation by lowering IL-11
for covid infection
