Steroid and Nuclear Hormone Receptor Superfamily of TFs Flashcards
What is nuclear hormone receptor superfamily?
- largest group if TFs in eukaryotes that are functionally and structurally similar
- ligand-regulated transcription factors
- activated by steroid hormones
short signal transduction pathway
types of NHR?
- Type 1 receptors (steroid)
- Type 2 receptors (thyroid hormone, vitamin D, lipid derivatives)
- Orphan receptors (unknown ligands)
type (ligand)
What is the 1º structure of NHR?
- N-terminus (transactivation domain) A/B
- DBD
- Hinge (flexibility + nuclear localization signal)
- LBD (activation domain)
- C terminus
What are type I: steroid receptors?
where is it found? how does it bind to DNA?
- when ligand activated, then undergo translocation
- bind as homodimers to inverted repeat DNA
What are type II: RXR heterodimers?
where is it found? how does it bind to DNA?
- always in nucleus
- binds as heterodimers with RXR to direct repeats of DNA in absence of ligand
hormone response elements feature (imperfect palindromic sequence) —- half sites with a
consensus sequence TGACCT in various arrangements
hexanucleotide
in direct repeat, everted or inverted repeat
steroid receptors have conserved region including
- DBD (NLS + Dimerization motif)
- Ligand binding domain
binds as homodimer, long A/B domain, binds palindromic half sites
mechanism of type 1 receptors?
- steroid hormone attaches to steroid receptor which has an inhibitor complex attached to it
- then the receptor goes to nucleus and attaches to another complex to make homodimer
mechanism of type 2 receptors?
- ligand binds to heterodimer which is already attached to response element by RXR
- uses corepressor (deacetylation) and coactivator (acetylation)
What is the structure of a DNA binding domain?
~ 70 residues
2 zinc containing regions where zinc is bound with 4 cysteines
How does the ligand binding domain work?
- ligand binding causes conformational change
- change affinity for protein
- expose AD
