Nuclear Receptors

Question 1

N-terminus

Answer 1

• Cell specific transcription factors bind to the AF1 region in order to alter receptor function
• binding of transcription factors to this region independent of ligand activity; ligand does not need to be bound for transcription factors to modify cell activity

Question 2

Core domain

Answer 2

• highly conserved region, amino acid structure is held in place by zinc fingers
• primary function is to bind to hormone response elements
• also has a role in regulating receptor dimerisation

Question 3

Hinge region

Answer 3

• allow for dimerisation with other NR’s, creating diverse configurations of the molecule to interact with DNA in varied manners

Question 4

C-terminus

Answer 4

• Highly conserved region
• contains ligand binding molecule
• where binding of molecular chaperone occurs

Question 5

Functionality of NR’s

Answer 5

• Ligand activated transcription factors that transduce signals by modifying gene transcription
• Function is informed by the unique structure of AF1 and AF2 domains which recruit other proteins to act as coactivators and corepressors

Question 6

HSP’s

Answer 6

• When bound to AF2 dimerisation is prevented and the nuclear localisation machinery is hidden

Question 7

HRE’s

Answer 7

• short sequences of DNA able to bind to a specific NR complex in order to regulate transcription

Question 8

Class 1

Answer 8

• predominantly consists of endocrine steroid receptors such as glucocorticoid receptors, mineral corticoid receptors, oestrogen receptors, progesterone receptors and androgen receptors
• Reside in cytosol when unbound, often conjugated with HSP’s
• binding of ligand results in exposition of dimerisation sequence, dimerisation occurs and the complex is translocated to the nucleus
• in the nucleus binding to HRE’s occurs to either activate or repress gene expression

Question 9

Class 2

Answer 9

• exists in the nucleus, bound to DNA and co-repressor proteins
• binding of ligand results in disassociation of repressors allowing activation of transcription factors
• almost exclusively heterodimers

Question 10

Differential gene control

Answer 10

• epigenetic changes in the DNA mean some genes cannot be activated in some tissues