Nuclear and Apoptotic Receptors Flashcards
How do nuclear receptors promote a biological effect?
By regulating transcription.
Where are steroid receptors present in the cell? What about thyroid hormone receptors?
Glucocorticoid: cytoplasm
Thryroid: nucleus
What 4 types of receptors make up the steroid receptor family?
- Glucocorticoid receptor
- Mineralocorticoid receptor
- Androgen receptor
- Progesterone receptor
What 6 types of receptors make up the thyroid receptor family?
- Thyroid hormone receptor
- Estrogen receptor
- Retinoic acid receptor
- Retinoic X receptor
- Peroxisome proliferator-activated receptor
- Vitamin D receptor
Which known steroid has a receptor which is part of the thyroid receptor family, rather than the steroid receptor family? Why?
Estrogen, because of receptor structural homology.
Are nuclear receptors soluble?
Yes, they are not membrane bound and can move about freely.
Besides steroid receptors and thyroid hormone receptors, what other category of receptors are there? What defines these?
“Orphan receptors” which have no known ligand.
What differentiates the ligands for nuclear receptors from the ligands of other receptors?
Nuclear receptor ligands are not proteins, but rather small hydrophobic molecules that diffuse across membranes.
What are the 3 domains which make up a nuclear receptor?
- Amino terminal domain
- DNA binding domain
- Ligand binding domain
What is the function of the nuclear receptor’s amino terminal domain?
Ligand-independent transactivation.
What are the functions of the nuclear receptor’s DNA binding domain? What characteristic structure is present here?
DNA binding and dimerization. The zinc fingers here make it possible for DNA to bind.
What are the functions of the nuclear receptor’s ligand binding domain?
Ligand binding, ligand-dependent transactivation. Also responsible for hetero/homo-dimerization as well as association with heat shock proteins and nuclear translocation.
What do mutations in the nuclear (thyroid) receptor’s ligand binding domain often cause?
Diseases from resistance to thyroid hormone (attention deficit to severe brain disorders)
What is the purpose of the AF-1 subdomain in nuclear receptors?
Alters the conformation of the receptor, changing ligand binding.
Do nuclear receptor ligands always bind to their receptors?
No, they can act alone and have non-genomic effects (thyroid hormone, steroid hormones)
What is the purpose of the “zinc finger” motif? How do they accomplish this?
Generally a pair of zinc fingers on the nuclear receptor. The first binds DNA while the second is involved in dimerization of the receptor.
What structure do steroid receptors assume upon ligand-binding? What thyroid hormone receptor mimics this? How are their recognition sequences arranged?
They bind as homodimers. Estrogen receptors also assume this conformation. Recognition sequences are palindrome/inverted repeats (ex: AGANNNTGT).
What structure do thyroid receptors assume upon ligand-binding? How are their recognition sequences arranged?
They bind as heterodimers (prefer 1 TR and 1 RXR). Recognition sequences are direct repeats (ex: TCANNNTCA) or palindrome/inverted repeats (ex: AGANNNTGT).
What is meant by the “mousetrap” in a nuclear hormone receptor? What does this structure do?
A phobic pocket in the receptor (12a-helices + 1b-turn) which can bind antagonists or agonists to control coactivator binding.
What 3 steps describe the corepression/coactivation of nuclear receptors?
- A repressor complex with histone deacetylases close chromatin
- While transcription is repressed, ligand binds and remodels chromatin (uses ATP)
- histone acetyltransferases reopen chromatin
What differentiates nuclear receptors from membrane receptors when comparing against blood binding protein?
The association with a membrane. Every other characteristic of receptors compared to blood binding protein still holds (specificity, affinity, saturability, etc).
What differentiates the roles of histone deacetylases (HDACs) from histone acetyltransferases (HATs)?
HDAC: closes chromatin, repressing transcription.
HAT: opens chromatin, activating transcription.
What are some examples of molecules which help promote cell proliferation?
Estrogen, testosterone, epidermal growth hormone, etc.
What differentiates an extracellular apoptotic signal from an intracellular apoptotic signal?
Extracellular: increased receptor expression on membrane signals the need for death to nearby cells
Intracellular: initiated at mitochondria (maybe by detecting shortening telomeres)
