Vital protein complex and therapeutic possibilities revealed
By By Scott LaFee, UC San Diego Health Sciences and Ian Demsky, University of Michigan Health System | 29 Sep 2011
The newly revealed molecular structure of G protein-coupled receptors illustrate the 29 September cover of Nature. The findings were the result of a multi-institutional collaboration that included UC San Diego.
 |
| The newly revealed molecular structure of G protein-coupled receptors illustrate the September 29 cover of Nature. The findings were the result of a multi-institutional collaboration that included UC San Diego. |
Three international teams of scientists, led by researchers at the University of California San Diego, University of Michigan and Stanford University, have published a trio of papers describing in unprecedented detail the structure and workings of G protein-coupled receptors (GPCRs), a large family of human proteins that are the target of one-third to one-half of modern drugs.
Two of the papers are published as cover-story articles in the September 29 print issue of the journal Nature. The third paper was published in the 12 September early online edition of the Proceedings of the National Academy of Sciences (PNAS).
GPCRs are essential to human life, involved in almost every physiological function. Located within the membranes of cells, these receptors detect arriving hormones, chemical neurotransmitters, odors and other signaling molecules, then activate internal G proteins, which, behaving like molecular switches, initiate other events that affect everything from the senses and behaviour to fundamental functions like heart rate and blood pressure. Malfunctions in these signaling pathways have been linked to dozens of diseases, including diabetes, blindness, asthma, depression and some forms of cancer.
''The 800 or so known GPCRs do an incredible variety of things, which is why they're broadly considered the most important target for new drugs,'' said Virgil Woods Jr., MD, a professor of medicine at UCSD School of Medicine and a co-author on two of the papers.
''But historically they've been very difficult to work with. We haven't had a good grasp of their precise structure and functioning. A lot of drugs are based on targeting GPCRs, but they're hit or miss. Until recently, we have known little about how GPCRs actually work at the sub-molecular level,'' Woods added.
.webp)
