Molecule Hedgehog transmits signals containing information embryonic cells. Lack of security during development leads to birth defects, while the runaway alarm occurs in many cases of cancer, such as basal cell carcinoma, brain cancer , breast cancer and prostate cancer.
Technology Cryo-EM microscopy revealed the molecular mechanism of Hedgehog signaling.
The presence of a better understanding of the structure could help pharmaceutical companies to develop drugs that are intended for normal signaling Hedgehog.
In a study published today in Science, the researchers UT Southwestern and Rockefeller University used modern microscopes to determine the atomic resolution structure of a molecular complex involved in birth defects and some cancers.
Signaling pathway that transmits information to embryonic cells, is crucial to human health. Lack of security during development leads to birth defects, while the runaway alarm occurs in many cases of cancer. Excessive signaling is associated with basal cell carcinoma - the most common malignant cancer in men - as well as cancer of the brain, breast cancer and prostate cancer, said Dr. Xiaochun Li, southwest assistant in molecular genetics and biophysics at the UT, as well as Rita K ., and William P. Clements, junior researcher in the field of biomedical research. Many pharmaceutical companies are developing drugs designed for alarm. Dr Lee said that a clearer understanding of the structure can help in this effort.
The researchers, using technology cryoelectron microscopy (cryo-EM) showed that two molecules Patched-1 (PTCH1) at the same time interact with one molecule Hedgehog (HH), but on two different sites. This unique set PTCH1-HH with a ratio of 2 to 1 is necessary for effective Hedgehog signaling in cells.
Cryo-EM uses enormous microscopes equipped robotics to determine the molecular structure of samples, which freeze at low temperatures so that the ice crystals can not be formed.
In another paper published in Nature last month, the group of Dr. Lee reported on Cryo-EM structure of the complex of 1-to-1 PTCH1-HH. Their biochemical analyzes showed that HH binding to one molecule PTCH1 may be insufficient to complete the activity. He said that HH, you may need to dial any other protein or other molecule PTCH1.
"In the current research paper we report on a set of 2-to-1 PTCH1-HH, in which one Hedgehog molecule binds to two of its receptors (PTCH1) at two different points. We used our analysis of cell biology, to ensure that the 2 1 st complex is indeed a signal generator for Hedgehog signaling. In conjunction with the earlier study, published in Nature, we hope that this new work will provide additional information for physicians and scientists in this field, "- he explained.
The study was supported by the Research Institute for the prevention of cancer of Texas (CPRIT), the program UT Southwestern Endowed Scholars in the field of medical sciences, the Foundation for young faculty O'Donnell Welch Foundation, the National Institutes of Health and the Rockefeller University.