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Determining The Structure Of Nuclear Receptor Has Implications For A Host Of Diseases

Date:
September 18, 2008
Source:
Public Library of Science
Summary:
Researchers have determined the molecular structure of a nuclear receptor, which regulates the expression of specific genes within cells, that may serve as a drug target for diseases related to heart and blood vessel development, human embryonic development and female infertility. Researchers also found that the receptor, named COUP-TFII, is activated by retinoic acid, a form of Vitamin A.

In a study published this week in PLoS Biology, Eric Xu and colleagues have determined the molecular structure of a nuclear receptor, which regulates the expression of specific genes within cells, that may serve as a drug target for diseases related to heart and blood vessel development, human embryonic development and female infertility. Researchers also found that the receptor, named COUP-TFII, is activated by retinoic acid, a form of Vitamin A.

"Not only does the structural information provide a basis for drug design in any diseases that COUP-TFII plays a role in, but it also can provide insight into the entire subfamily of receptors that COUP-TFII belongs to, which could have implications for additional associated diseases," said Xu, who heads the laboratory that published the findings.

The researchers determined the molecular structure of COUP-TFII through X-ray crystallography, which involved purifying the protein, growing crystals, directing X-rays at the crystals, and using the resulting information to determine the structure. Structural information can help drug developers fit therapeutics more perfectly to the receptors they bind to for maximum potency and can also aid in manipulating drugs to produce fewer side effects.

The findings could also have implications for cancer therapy. "Since COUP-TFII plays a role in embryonic blood vessel development, it might play a similar role in tumors and cancer growth," said Schoen Kruse, lead author of the study. "Formation of new blood supply in tumors is a stepping stone in the ability of cancers to grow and metastasize within the body."

The signal-triggering molecules known as ligands, which activate nuclear receptors have been discovered for most receptors, but not for a subset of "orphan" nuclear receptors whose ligand remains unknown. The study's finding that COUP-TFII is activated by retinoic acid is significant since the receptor previously belonged to this subset of "orphan" receptors.


Story Source:

The above story is based on materials provided by Public Library of Science. Note: Materials may be edited for content and length.


Journal Reference:

  1. Kruse SW, Suino-Powell K, Zhou XE, Kretschman JE, Reynolds R, et al. Identification of COUP-TFII Orphan Nuclear Receptor as a Retinoic Acid%u2013Activated Receptor. PLoS Biol, 2008; 6(9): e227 DOI: 10.1371/journal.pbio.0060227

Cite This Page:

Public Library of Science. "Determining The Structure Of Nuclear Receptor Has Implications For A Host Of Diseases." ScienceDaily. ScienceDaily, 18 September 2008. <www.sciencedaily.com/releases/2008/09/080916101154.htm>.
Public Library of Science. (2008, September 18). Determining The Structure Of Nuclear Receptor Has Implications For A Host Of Diseases. ScienceDaily. Retrieved October 20, 2014 from www.sciencedaily.com/releases/2008/09/080916101154.htm
Public Library of Science. "Determining The Structure Of Nuclear Receptor Has Implications For A Host Of Diseases." ScienceDaily. www.sciencedaily.com/releases/2008/09/080916101154.htm (accessed October 20, 2014).

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