1hcp
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DNA RECOGNITION BY THE OESTROGEN RECEPTOR: FROM SOLUTION TO THE CRYSTAL
OverviewOverview
BACKGROUND: The steroid/nuclear hormone receptors are a large family of, conserved ligand-activated transcription factors that regulate gene, expression through binding to response elements upstream of their target, genes. Most members of this family bind to DNA as homodimers or, heterodimers and recognize the sequence, spacing and orientation of the, two half-sites of their response elements. The recognition and, discrimination of the sequence and arrangements of these half-sites are, mediated primarily by a highly conserved DNA-binding domain. RESULTS: Here, we describe the DNA-binding properties of the isolated DNA-binding domain, of the oestrogen receptor, the ERDBD, and its refined NMR structure. This, domain is monomeric in solution, but two molecules bind cooperatively to, specific DNA sequences; this cooperativity determines the arrangement of, half-sites that is recognized by the ERDBD. The 10 carboxy-terminal, residues and a region of 15 residues within the domain are disordered in, the solution structure, yet are important for DNA binding. CONCLUSION: The, cooperative nature of ERDBD binding to DNA is important. The, previously-determined X-ray structure of the ERDBD dimer bound to DNA, shows that the 15 internal residues disordered in solution make contact, both with DNA and with the corresponding region of the other monomer., These results suggest that these residues become ordered during the, process of binding to DNA, forming the dimer interface and thus, contributing to the cooperative interaction between monomers.
DiseaseDisease
Known diseases associated with this structure: Atherosclerosis, susceptibility to OMIM:[133430], Breast cancer OMIM:[133430], Estrogen resistance OMIM:[133430], HDL response to hormone replacement, augmented OMIM:[133430], Migraine, susceptibility to OMIM:[133430], Myocardial infarction, susceptibility to OMIM:[133430]
About this StructureAbout this Structure
1HCP is a Single protein structure of sequence from Homo sapiens with ZN as ligand. Full crystallographic information is available from OCA.
ReferenceReference
DNA recognition by the oestrogen receptor: from solution to the crystal., Schwabe JW, Chapman L, Finch JT, Rhodes D, Neuhaus D, Structure. 1993 Nov 15;1(3):187-204. PMID:16100953
Page seeded by OCA on Mon Nov 12 17:15:59 2007