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bio 211 > lecture 3 > Flashcards

lecture 3 Flashcards

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Biology 101 flashcards
1
Q

how many molecules do GPCR ligands encompass/recognize

A

huge variety

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2
Q

examples of ligands GPCRs recognize

A

peptides, steroid hormones, smell, sight, etc.

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3
Q

how many times does GPCR pass thru membrane

A

7 times

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4
Q

describe inactive receptor

A

not bound to anything; no kinase, no enzymatic characteristics

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5
Q

describe heterotrimeric G proteins

A

not bound to receptor, hanging out in the vicinity b/c bound to each other

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6
Q

what has lipid anchors

A

2 members of heterotrimeric complex; so anchored to plasma membrane

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7
Q

why are they anchored to memrbane

A

close proximity to receptor

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8
Q

what happens when GPCR is activated

A

signaling molecule binds it

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9
Q

what does molecule binding to receptor cause

A

conformational change in G receptor allowing it to bind to heterotrimeric complex

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10
Q

what specific part of heterotrimeric complex does G receptor bind to

A

G alpha

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11
Q

what does activation of G alpha cause

A

heterotrimeric G protein to dissociate (it’s active now)

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12
Q

what happens to G protein

A

dissociates, moves along plane of plasma membrane to activate downstream proteins

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13
Q

what is brown blob

A

adenylyl cyclase (enzyme, now activated)

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14
Q

what do trimeric G proteins do

A

relay signals from GPCRs

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15
Q

where are trimeric G proteins associated

A

w/ inner leaflet of plasma membrane

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16
Q

describe inactive form of heterotrimeric G complex

A

only G alpha is bound to GDP

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17
Q

what does G alpha bound to GDP repesent

A

inactive form; GDP means off

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18
Q

where is G alpha anchored

A

plasma membrane

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19
Q

where is G gamma anchored

A

plasma membrane

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20
Q

where is beta

A

helps hold alpha and gamma together in off form

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21
Q

what happens when GPCR is activated

A

it acts like a GEF and triggers activation of its associated G protein

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22
Q

what happens when signaling molecule arrives

A

conformational change in GPCR

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23
Q

example of conformational change

A

loop on cytoplasmic face unfolds; activation dependent conformational change

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24
Q

what does activation dependent conformational change allow

A

allows it to bind and activate G alpha

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25
Q

what is that activation

A

GPCR is gonna act as a guanine exchange factor

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26
Q

what is above mechanism

A

mechanism of activation of G alpha

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27
Q

what does GEF do

A

kicks off GDP, replaces it with GTP

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28
Q

what happens to alpha when activated

A

G alpha dissociates from beta gamma, floats freely

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29
Q

what happens to beta and gamma

A

remain stuck together; they are also activated

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30
Q

what happens to GPCR

A

remains activated; if any other copies of inactive form of heterotrimeric G protein complex its gonna bind and activate them until ligand is gone / pathway desensitized

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31
Q

where is the signaling happening at this step of pathway

A

at plasma membrane (b/c GPCR is in plasma membrane)

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32
Q

what does phosphorylated mean

A

activated

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33
Q

what do lipid anchors do

A

hold proteins at certain locations

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34
Q

what do some G proteins do

A

regulate production of cyclic AMP

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35
Q

what happens after G alpha becomes activated by exchanging GDP for GTP

A

it activates adenylyl cyclase

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36
Q

what does adenylyl cyclase do

A

converts ATP into a cyclized version called cyclic AMP

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37
Q

KNOW

A

adenylyl cyclase is responsible for converting ATP to cAMP

38
Q

what does cAMP act as

A

second messenger; binds and activates downstream proteins to propagate signal further into cell

39
Q

is cAMP a protein or chemical

A

chemical

40
Q

how do we get rid of cAMP

A

phosphodiesterase; converts cyclic AMP to AMP

41
Q

why does converting cAMP to AMP work

A

AMP is nolonger capable of signaling

42
Q

what does adenylyl cyclase do

A

converts ATP to cAMP

43
Q

what does cAMP do

A

allows signal propagation

44
Q

what does phosphodiesterase do

A

destroys cAMP & turns off pathway

45
Q

what mediates most of the effects of cyclic AMP

A

cyclic AMP dependent protein kinase (PKA)

46
Q

describe cAMP molecule

A

small, water soluble; good at diffusing thru cytoplasm but can’t cross lipid bilayers

47
Q

what part of step is at lipid membrane

A

GPCR (transmembrane protein), G alpha and beta-gamma (cuz of lipid anchor) adenylyl cyclase

48
Q

how does adenylyl cyclase meet G alpha

A

they’re all stuck at plasma membrane so that’s where they meet

49
Q

where does cAMP go

A

free to diffuse into cytoplasm [departure point from membrane]

50
Q

what is cAMP’s target

A

protein kinase A / PKA

51
Q

describe inactive PKA

A

cytoplasmic protein (not associated w/ membranes)

52
Q

describe structure of PKA

A

tetramer: 2 regulatory subunits, 2 catalytic subunits

53
Q

what do PKA regulatory subunits do

A

when bound to catalytic subunits, they regulate them and hold them off –> PKA off

54
Q

describe PKA off

A

2 regulatory subunits bound to catalytic subunit

55
Q

what does cAMP do when diffuses through cytoplasm

A

binds to catalytic subunit

56
Q

how many molecules of cAMP needed to activate 2 copies of PKA

A

4 molecules of cAMP to activate 2 copies of PKA

57
Q

describe this signaling step

A

reduction instead of amplification

58
Q

give examples of amplification in steps

A

one GPCR activates several g alpha proteins which activate several adenylyl cyclases, create hundreds of thousands of copies of cAMP [each step gets more and mroe abundant]

59
Q

what happens when cAMP binds to regulatory subunit

A

activates pKA, releases it from regulatory subunits

60
Q

what does activated PKA do

A

phosphorylates downstream targets in nucleus

61
Q

what do Gs proteins do

A

generation of cyclic AMP and PKA activation

62
Q

describe transport in and out of nucleus

A

highly regulated, activation dependent

63
Q

what does activation of PKA do for nucleus

A

represents mechanism to get signaling across nuclear pore and into nucleus & change gene transcription

64
Q

where does PKA go when activated

A

enters nucleus thru nuclear pore

65
Q

what is end goal of PKA

A

change gene transcription

66
Q

how many copies of PKA enter nucleus

A

2 copies

67
Q

what does PKA do when in nucleus

A

phosphorylates creb protein

68
Q

what does phosphorylation of CREB do

A

when activated CREB initiates transcription of target gene

69
Q

what is output of PKA pathway

A

change in gene regulation

70
Q

how does PKA changing gene regulation happen

A

g alpha activates adenylyl cyclase, converts ATP to cAMP, activates PKA, enters in nucleus, phosphorylates CREB and activates it which activates target gene transcription

71
Q

what was the Gs subunit dependent on

A

adenylyl cyclase

72
Q

name another GPCR pathway

A

some G proteins signal via phospholipids

73
Q

what happens when GPCR becomes activated

A

G alpha protein is activated

74
Q

what does activated G alpha do

A

binds and activates phospholipase c-B

75
Q

what does phospholipase c-B do

A

cleaves PI 4,5-bisphosphate into diacylglycerol and IP3 (inositol 1,4,5-trisphosphate)

76
Q

where does diacylglycerol remain

A

embedded in plasma membrane

77
Q

describe structure of diacylglycerol

A

head group is polar and water soluble

78
Q

where does IP3 go

A

into endoplasmic reticulum

79
Q

what G protein is for adenylyl cyclase pathway

A

G alpha S

80
Q

what G protein is for phospholipase pathway

A

G alpha q

81
Q

how do we distinguish these two pathways

A

by the specific G protein being activated

82
Q

why is calcium kept in ER and out of cytoplasm

A

very potent second messenger; kinda like cAMP would just bind and activate shit

83
Q

describe structure of IP3

A

polar head group of PIP2

84
Q

what happens once IP3 when cleaved

A

nothing holds it to plasma membrane so it diffuses to cytoplasm

85
Q

what does IP3 see in cytoplasm

A

ion gated receptor activated by ligand binding in ER membrane

86
Q

what happens when IP3 binds channel

A

its a calcium channel, so when IP3 binds it floods calcium from ER into cytoplasm & triggers signaling

87
Q

what does IP3 do w/ DAG

A

cooperates w/ diacylglycerol to activate protein kinase C, further downstream steps

88
Q

what do all GPCRs activate

A

Galpha subunits to trigger downstream signaling

89
Q

what can GPCRs do to target gene transcriptoin

A

activate cAMP production

90
Q

what can GPCRs do for calcium

A

open IP3 gated channels in ER to trigger calcium signaling

bio 211 (18 decks)

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