PP #2

Question 1

Hinge region

Answer 1

• A flexible domain connecting DBD with LBD
• Influences intracellular trafficking and
  subcellular distribution

Question 2

Ligand binding domain (LBD):

Answer 2

• Moderately conserved in sequence, highly conserved in structure between
  nuclear receptors.
• Contributes to the dimerization interface of the receptor
• Binds coactivator/corepressor proteins

Question 3

PTX

Answer 3

blocks cataylsis of GTP exchange = Ga subunit remains in GDP unactive state

Question 4

CTX

Answer 4

inhibits GTPase activity of a subunit causing Ga subunit to remain in actived form GTD

Question 5

Cytosolic or nuclear (intracellular) receptors pathway

Answer 5

(1) Hormone binding changes conformation of receptor protein
* Causes inhibitory protein (heat shock protein HSP) complex to dissociate
* Causes receptor (LBD) to bind to coactivator proteins  induce gene transcription
(2) Interact with DNA of chromosomes
* Initiates mRNA synthesis (transcription) and protein synthesis (translation)
* Slower response (genomic and synthetic events require time).

Question 6

Types of Membrane receptors

Answer 6

Ligand gated ion-channel receptors
Receptor kinases (receptors that are enzymes)
Receptors associated with enzymes
G protein-coupled receptors (GPCR)

Question 7

GPCR

Answer 7

G protein-coupled receptors

Question 8

Autophosphorylation (in kinase receptors)

Answer 8

Binding of the ligand to the receptor alters the receptor’s shape, which activates its enzyme function, phosphorylating an intracellular protein

Question 9

Receptor tyrosine kinases (RTK):
contains:

Answer 9

• Extracellular ligand-binding domain
• Single transmembrane spanning domain
• Intracellular kinase domain

Question 10

RTK Mechanism of action

Answer 10

Receptor must dimerize in order to become phosphorylated and activate intracellular signaling molecules > cross-phosphorylation.

Question 11

RTK Mechanism of action

Answer 11

Receptor must dimerize in order to become phosphorylated and activate intracellular signaling molecules > cross-phosphorylation.

Question 12

GPCR Transducers:
Turnover cycle

Answer 12

(1) Hormone‐receptor binding  conformational change in receptor
(2) interaction of receptor with G protein
(3) GDP dissociates from α subunit, GTP binds to α subunit  disassembly of G protein - α subunit dissociates from β/γ subunits
(4) G Protein α subunit bind to effectors (e.g. adenylyl cyclase)
Second messenger activation (converts ATP to cAMP)
Second messenger (cAMP) activates intracellular enzymes (e.g. kinases) to change cell function
(5) GTP is hydrolyzed to GDP  G protein α subunits dissociate from effectors, regenerate G protein.
Hormone required for another cycle to proceed.

Question 13

5 criteria determine if hormone’s effect is mediated by cAMP

Answer 13

Hormones should:
stimulate adenylyl cyclase
Increase cAMP before or concurrently with its effects
Analog show correlation between elevate cAMP and effects
Drugs that inhibit phosphodiesterase activity should mimic hormone effects
Exogenous cAMP mimic hormone effects