Chemistry Nobel Prize awarded to receptor biologists
U.S. researchers at Duke and Stanford honored for their work on G protein-coupled receptors
The Royal Swedish Academy of Sciences announced today that the Nobel Prize in Chemistry was awarded jointly to Robert J. Lefkowitz and Brian K. Kobilka for their work with G protein-coupled receptors (GPCRs). Lefkowitz and Kobilka, professors at Duke University and Stanford University respectively were recognized for their contribution in identifying and mapping out the GPCRs in “finest molecular detail.”
Proteins, often called the basic building blocks of life, serve a variety of functions in the human body — including as hormone signal receptors. GPCRs, which are present ubiquitously and control a myriad of bodily functions, are embedded in cell walls. When there is a change in hormone level outside the cell, the receptor changes its physical form to bind with specific chemicals within the cell, which then bring about the appropriate cellular response.
Lefkowitz, who has said to have had a “real eureka moment” when he realized that there was a whole superfamily of homological proteins, was the first scientist to radioactively label the GPCRs in the plasma membrane in the 1960s. Almost two decades later, Kobilka joined Lefkowitz’s research team and isolated the gene that codes for a specific GPCR from the human genome. Feeding off of each other, Kobilka and Lefkowitz have since independently and collaboratively worked on different aspects of the structure and functioning of GPCRs.
Their discovery has astounding medical implications since almost 50 percent of all drugs work by targeting such receptors and manipulating their response. For instance, an increased level of histamine in the body will cause GPCRs to change their structure in the cell wall, which causes fluid from cells of capillaries to escape to the surrounding tissue. This leads to inflammation. An anti-histamine drug works by preferentially attaching itself to the receptors that would normally be affected by histamine. Hence, by blocking histamine from reaching its receptor, the drug prevents the leaking of cell fluid and consequent inflammation.
Kobilka, who recently revealed the 3D structure of a specific receptor bound to its protein, once worked as a post-doctoral fellow with Lefkowitz. They will be sharing the prize money of eight million kronor ($1.2 million).
Lefkowitz who spoke to the press and committee members immediately after the announcement said the award came as a “total shock and surprise.”