Washington, October 30 : Scientists have unveiled a detailed, three-dimensional structure of the beta2-adrenergic receptor protein, which hails from a family of proteins called G protein-coupled receptors (GPCRs) that control critical bodily functions, several of human senses, and the action of about half of the pharmaceuticals.

Raymond Stevens and co-workers of The Scripps Research Institute say that being the first known structure of a human GPCR, their work promises not only to speed the discovery of new and improved drugs, but also to broaden scientists’ understanding of human health and disease.

The research was supported by two major initiatives of the National Institutes of Health—the NIH Roadmap for Medical Research and the Protein Structure Initiative (PSI), which is led by the National Institute of General Medical Sciences.

In order to solve the new structure, the researchers overcame daunting scientific obstacles, many of which arise because GPCRs are membrane proteins that are known to resist forming crystals, which are needed for structure determination.

“Because of their role in so many medically important processes and the great challenges they present for detailed study, membrane proteins have been one focus of the NIH Roadmap. The determination of this structure is an exciting example of the rewards from the Roadmap investment,” said Dr. Elias A. Zerhouni, NIH Director.

Scientists across the country have tried for years to obtain detailed images of GPCR proteins, and they have succeeded only once before, in 2000, when a research group determined the structure of a visual pigment in cow eyes.

In order to overcome problems with the protein’s floppiness, the researchers replaced a flexible loop with a more rigid protein structure.

Raymond Stevens’ team managed to coax the intransigent proteins into tiny crystals by devising techniques and environmental conditions that mimicked the protein’s native, membrane-like environment.

The researchers say that the genetic engineering and crystallization techniques may be broadly applicable to similar proteins, paving the way for more structures from the hundreds of GPCRs encoded in the human genome.

“This is an absolutely remarkable advance,” said Dr. Jeremy M. Berg, director of NIGMS, which, in addition to spearheading the PSI, plays a leading role in the membrane protein Roadmap initiative.

“Many laboratories around the world are trying to reveal the secrets of these proteins, and this important structure takes the field to a higher level,” Dr. Berg added.

The research has been described in the journal Science Express. (ANI)