Lecture 8: Hormone Receptors Flashcards Preview

SMP - MNE Exam 1 > Lecture 8: Hormone Receptors > Flashcards

Flashcards in Lecture 8: Hormone Receptors Deck (81):
1

What are the 7 domains of a nuclear hormone receptor?

1. Hormone binding
2. DNA binding
3. Nuclear localization
4. Dimerization/Modulation/Phosphorylation domains
5. Transducing domain

2

What are the 6 domains of a membrane hormone receptor? Which ones are in the cell and which ones are out?

1. Hormone binding (out)
2. Transmembrane (within)
3. Dimerization (out)
4. Modulation (in)
5. Phosphorylation (in)
6. Transducing domain (in)

3

What are the 4 ways for a membrane hormone receptor to trigger a second messenger system?

1. Dimerization
2. Modulation
3. Phosphorylation domains
4. Enzymatic activity

4

What method is used by membrane receptors to induce a conformational change leading to transduction of response/second messenger cascade?

Dimerization

5

Which is inside the cell: N or C terminus of membrane hormone receptor?

Depends!

6

Where is the hormone-binding domain of nuclear hormone receptors? What is particular about it?

At the C-terminal
LARGE: ~250 AAs

7

What is the function of the nuclear localization domain of the nuclear hormone receptor?

Allows receptor to localize the nucleus of the cell

8

When does the nuclear hormone receptor enter the nucleus?

Could have always been there or upon binding to the hormone in the cytosol

9

What is the transducing domain of the nuclear hormone receptor?

Could be considered the entire hormone receptor

10

What is an agonist?

Molecule that binds to the hormone receptor and brings about a response

11

What is an antagonist?

Molecule that binds to the hormone receptor and inhibits the agonist responses

12

What is the role of the transducing domain of the membrane hormone receptor? What part of the receptor is it?

To induce second messengers
Cytoplasmic side of the receptor

13

What is the role of the transducing domain of the nuclear hormone receptor?

Activate transcription

14

Which bind better: agonists or antigonists?

Agonists usually

15

How can one determine if the binding domain of a hormone receptor binds the hormone reversibly?

Binding assay: scatchard plots

16

Which type of receptors can be glycosylated?

Membrane receptors

17

Which type of membrane receptors can have enzymatic activity??

Membrane receptors

18

What is an example of a partial/weak antagonist?

Ru486: works to inhibit progesterone receptor but partially inhibits the glucocorticoid receptor

19

What can an antagonist's properties depend on? Example?

The tissue it is in!
Eg: tamoxifen inhibits estradiol receptors well in breasts and poorly in bone

20

What does hGR stand for?

Glucocorticoid receptor

21

What does hMR stand for?

Mineralcorticoid receptor

22

What does hAR stand for?

Androgen receptor

23

What does hPR stand for?

Progesterone receptor

24

What does hERalpha and B stand for?

Alpha and beta estrogen receptors

25

What does hTR stand for?

Thyroid receptor

26

What are the 2 main types of hTRs?

Alpha 1 and beta 1

27

What does hRAR stand for?

Retinoic acid receptor

28

What are the 3 types of hRARs?

Alpha, beta, gamma

29

What does hRXR stand for?

Retinoic acid X receptor

30

What are the 3 types of hRXRs?

Alpha, beta, gamma

31

What does hPPAR stand for?

Perioxosime proliferator

32

What do hPPARs regulate?

Lipid metabolism

33

What are the 3 types of hPPARs?

Alpha, beta, gamma

34

What does hVDR stand for?

Vitamin D receptor

35

What are the 3 groupings of nuclear receptors? What do they each share?

1. Steroid receptors: hGR, hMR, hAR, hPR

2. Estrogen receptors: hER alpha and beta

3. Others: hTR (alpha 1 and beta 1), hRAR alpha, hRXR alpha, hPPAR alpha, hVDR

They share P-box sequences

36

What % range AA homology between the hormone binding domains of nuclear receptors? But...?

15-50%
But conserved structure between all of them.

37

Describe the common structure of hormone binding domains of nuclear receptors? How come they all have it?

11-12 alpha helices arranged like a 3 layer sandwich with a hydrophobic hole/pocket
Helix 12 is the last helix at the C-terminus with 2 surfaces and is separate from the sandwich: hydrophobic (toward hormone) and hydrophilic --> the hydrophilic one interacts with coactivator proteins to regulate transcription

Evolution!

38

Describe the mechanism by which nuclear receptors bind hormones.

1. Hormone binds and causes all of the helices to crunch together: huge conformational change = induced fit
2. Helix 12 seals the binding cavity and exposes its hydrophilic surface to regulate transcription

39

What is the N terminal of nuclear hormone receptors often involved with?

Transcriptional activation and nuclear localization

40

Describe the structure of the DNA binding domain of nuclear hormone receptors. Where is it located?

2 zinc fingers + 2 alpha helices in a globular structure
Located in the center of the molecule

41

What part of the DNA binding domain of nuclear hormone receptors interacts with the DNA? 3 names

The first zinc finger = P-box = recognition helix

42

How would changing the P-box sequence affect binding of nuclear hormone receptor to DNA?

Would change the binding specificity

43

Can the hormones activating the nuclear receptors that have the same P-box activate all of them?

NOPE, more complicated than that BUT they could bind to the same DNA binding site

44

How do ALL hormones bind to nuclear receptors?

As DIMERS to DOUBLE-STRANDED DNA

45

What DNA sequence do steroid receptors bind?

Palindrome sequence separated by any 3 nucleotides

46

What DNA sequence do estrogen receptors bind?

Palindrome sequence separated by any 3 nucleotides

47

What 2 DNA sequences do thyroid receptors bind?

1. Palindrome sequence not separated by nucleotides
2. Direct repeats separated by any 4 nucleotides

48

What DNA sequence do VDRs bind?

Direct repeat separated by any 3 nucleotides

49

What DNA sequence do RARs bind?

Direct repeat separated by any 5 nucleotides

50

Which DNA sequences bind nuclear hormone receptors more tightly and with high affitiny: direct repeats or palindromes?

Palindromes

51

How is steroid receptor binding to DNA regulated?

Heat Shock Proteins are bound to the hormone binding domain of the receptor and are released upon hormone binding

52

What is the main Heat Shock Protein used to regulate steroid receptor binding to DNA?

HSP90

53

What is the receptor binding site sequence of the transcriptional coactivators?

LLxxLL
L: leucine
x: any AA

54

Do TRs need hormones to bind DNA?

Not necessarily

55

How is thyroid receptor activation of DNA transcription regulated?

Suppressor proteins that are released upon hormone binding due to a conformational change and coactivators bind

56

What molecules can bind hPPARs?

Arachidonic acid metabolites

57

What molecules bind hRARs?

All-trans retinoic acids

58

What molecules bind hRXRs?

9-cis retinoic acid

59

What is the main role of hRXRs? With which receptors?

Form heterodimers with other nuclear receptors
All except for steroid receptors: PPAR, RAR, TR, and VDR

60

What does the dissociation constant of a hormone correspond to?

The concentration of hormone that half saturates the receptor

61

What is equation to calculation the amount of hormone bound to a receptor?

Hormone bound = Max . [hormone] / Kd + [hormone]

Max = maximum possible hormone binding

62

When is regulation of the hormone binding to the receptor most powerful?

Around the Kd of that hormone

63

What is the purpose of a Stachard plot?

To find Kd

64

What are the 2 points to know on a Stachard plot?

1. Slope = -1/Kd
2. x-intercept = # of binding sites (or receptors if only 1 binding site per receptor)

65

What does a steeper slope on a Stachard plot mean?

Tighter binding

66

What does a curve instead of a line on a Stachard plot mean?

Concentration is very far from the Kd OR receptors with different affinities to a hormone

67

Which receptor is used for comparison to all the others?

hGR

68

What allows the common structure of the hormone binding domain of nuclear receptors to bind different hormones?

The induced fit nature of it

69

Describe the specificity of the DNA binding domain of nuclear receptors.

Low DNA binding specificity (only 66 amino acids in this region). But the P box forms alpha helices that will enter the major grooves of DNA. Some of these alpha helices are important for specificity

70

How do most transcription factors interact with DNA?

By entering the major grooves

71

Which nuclear receptors can bind DNA as homodimers very EASILY?

Those that have palindromic DNA binding sequences: GR, MR, PR, AR, ER (all the steroid receptors), TR

72

What is the direct repeat DNA binding sequence used for in nuclear receptors?

Hetero OR homodimers

73

Why do different nuclear receptors have different spacing between their DNA binding sequences?

To make room for the different nuclear receptor

74

Why is it very easy to get mutations in the androgen receptor?

Because it's X-linked

75

What is the Type 1 GR?

MR

76

What is the Type 2 GR?

GR

77

Type 2 diabetes drugs that increase the sensitivity to insulin target which type of nuclear receptors?

PPAR gamma

78

What are the 2 axis of a Statchard plot?

1. x-axis: bound
2. y-axis: bound/free

79

What are the 2 axis of a hormone binding curve? What shift shows tighter binding?

1. x-axis: log [hormone]
2. y-axis: relative binding

LEFT SHIFT

80

What domain of the nuclear receptor determines what subclass the receptor belongs to?

DNA binding domain

81

What is the role of the 2 zinc fingers? Do they interact with the DNA?

To situate the P box in the right major groove of DNA
They do not interact with the DNA