Determining the structure of nuclear receptor has implications for a host of diseases

Sep 16, 2008

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.

Citation: Kruse SW, Suino-Powell K, Zhou XE, Kretschman JE, Reynolds R, et al. (2008) Identification of COUP-TFII Orphan Nuclear Receptor as a Retinoic Acid–Activated Receptor. PLoS Biol 6(9): e227. doi:10.1371/journal.pbio.0060227 dx.plos.org/10.1371/journal.pbio.0060227

Source: Public Library of Science

Explore further: Mycobacteria metabolism discovery may pave way for new tuberculosis drugs

add to favorites email to friend print save as pdf

Related Stories

Ex-Qualcomm exec pleads guilty to insider trading

3 hours ago

A former high-ranking executive of US computer chip giant Qualcomm pleaded guilty Monday to insider trading charges, including trades on a 2011 deal for Atheros Communications, officials said.

Media venture creates press litigation fund

3 hours ago

The media venture created by entrepreneur Pierre Omidyar said Monday it was establishing a fund to help defend journalists in cases involving freedom of the press.

'Moral victories' might spare you from losing again

4 hours ago

It's human nature to hate losing. Unfortunately, it's also human nature to overreact to a loss, potentially abandoning a solid strategy and thus increasing your chances of losing the next time around.

Recommended for you

Report on viruses looks beyond disease

2 hours ago

In contrast to their negative reputation as disease causing agents, some viruses can perform crucial biological and evolutionary functions that help to shape the world we live in today, according to a new report by the American ...

User comments : 0