Ligand Binding Domain The LBD participates in several activities including hormone binding, homo- and/or heterodimerization, formation of the heat-shock protein complex and transcriptional activation and repression. The binding of the hormone induces conformational changes that seem to control these properties and influence gene expression. The conformational changes that accompany the transition between the liganded and unliganded forms of the nuclear hormone receptors affect dramatically their affinity for other proteins. In order to understand the functional role of the hormone one must understand the binding mechanism by which the hormone induces conformational changes.
Nuclear Hormone Receptor
DNA binding domainThe central DBD is responsible for targeting the receptors to their hormone response elements (HRE). The DNA binding domain, classified as a type-II zinc finger motif, has two subdomains, each containing a zinc ion coordinated by four cysteine residues, followed by an alpha-helix. The DBD binds as a dimer with each monomer recognizing a six base pair sequence of DNA. The reading helix of each monomer makes sequence specific contacts in the major groove of the DNA at each half-site. These contacts allow the dimer to read the sequence, spacing and orientation of the half-sites within its response element, and thus discriminate between sequences. These proteins exhibit, however, a flexibility in recognizing DNA sequences and also accept a variety of amino-acid substitutions in their reading helix without abolishing binding.
Heat shock proteins (HSP)
Heat shock proteins (HSP) are a group of proteins whose expression is increased when the cells are exposed to elevated temperatures or other stress. This increase in expression is transcriptionally regulated. This dramatic upregulation of the heat shock proteins induced mostly by Heat Shock Factor (HSF) is a key part of the heat shock response.
chaperones
In molecular biology, chaperones are proteins that assist the non-covalent folding/unfolding and the assembly/disassembly of other macromolecular structures, but do not occur in these structures when the latter are performing their normal biological functions. The common perception that chaperones are primarily concerned with protein folding is incorrect. The first protein to be called a chaperone assists the assembly of nucleosomes from folded histones and DNA and such assembly chaperones, especially in the nucleus, are concerned with the assembly of folded subunits into oligomeric structures.
hormone response element (HRE)
A hormone response element (HRE) is a response element for hormones, a short sequence of DNA within the promoter of a gene that is able to bind a specific hormone receptor complex and therefore regulate transcription.[1] The sequence is most commonly a pair of inverted repeats separated by three nucleotides, which also indicates that the receptor binds as a dimer.
retinoid X receptor (RXR)
The retinoid X receptor (RXR)[1] is a type of nuclear receptor which is activated by 9-cis retinoic acid.[2] There are three retinoic acid receptors (RXR), RXR-alpha, RXR-beta, and RXR-gamma encoded by the RXRA, RXRB, RXRG genes respectively.
Heat shock proteins (HSP)
Heat shock proteins (HSP) are a group of proteins whose expression is increased when the cells are exposed to elevated temperatures or other stress. This increase in expression is transcriptionally regulated. This dramatic upregulation of the heat shock proteins induced mostly by Heat Shock Factor (HSF) is a key part of the heat shock response.
chaperones
In molecular biology, chaperones are proteins that assist the non-covalent folding/unfolding and the assembly/disassembly of other macromolecular structures, but do not occur in these structures when the latter are performing their normal biological functions. The common perception that chaperones are primarily concerned with protein folding is incorrect. The first protein to be called a chaperone assists the assembly of nucleosomes from folded histones and DNA and such assembly chaperones, especially in the nucleus, are concerned with the assembly of folded subunits into oligomeric structures.
hormone response element (HRE)
A hormone response element (HRE) is a response element for hormones, a short sequence of DNA within the promoter of a gene that is able to bind a specific hormone receptor complex and therefore regulate transcription.[1] The sequence is most commonly a pair of inverted repeats separated by three nucleotides, which also indicates that the receptor binds as a dimer.
retinoid X receptor (RXR)
The retinoid X receptor (RXR)[1] is a type of nuclear receptor which is activated by 9-cis retinoic acid.[2] There are three retinoic acid receptors (RXR), RXR-alpha, RXR-beta, and RXR-gamma encoded by the RXRA, RXRB, RXRG genes respectively.
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