Brian K. Kobilka and G-protein-coupled Receptors (GPCR)

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Brian K. Kobilka
Credit: Linda A. Cicero
Stanford News Service

'Thanks in part to research performed at the U.S. Department of Energy’s (DOE) Argonne National Laboratory, the 2012 Nobel Prize in Chemistry was awarded today to Americans Brian Kobilka and Robert Lefkowitz for their work on G-protein-coupled receptors.

G-protein-coupled receptors, or GPCRs, are a large family of proteins embedded in a cell’s membrane that sense molecules outside the cell and activate a cascade of different cellular processes in response. They constitute key components of how cells interact with their environments and are the target of nearly half of today’s pharmaceuticals. ...

In a study performed at Argonne in 2007, Kobilka, a professor at Stanford University, used intense X-rays produced by the laboratory’s Advanced Photon Source (APS) to make the first discovery of the structure of a human GPCR. This receptor, called the human β2 adrenoreceptor (β2AR), is responsible for a number of different biological responses, including facilitating breathing and dilating the arteries.

A second and potentially even more exciting breakthrough occurred just last year, when Kobilka used the APS to determine the structure of β2AR at the exact moment that the protein-receptor complex signals across the membrane. This study represented the first time that a GPCR had been caught “in the act” of carrying out its biological mission. ...

In order to obtain the structure of a GPCR, Kobilka and his colleagues turned to X-ray crystallography, a process that can locate each of the atoms within a larger molecule such as a GPCR. “The combination of intense X-rays and cutting-edge crystallography capabilities at the APS gave the researchers a world-class tool tailored especially for this kind of experiment,” said APS associate laboratory director Brian Stephenson. “There are very few places in the world where these breakthroughs could have been made.”

“Argonne leads the world when it comes to developing and providing access to new crystallographic instruments and techniques,” Kobilka said last year.'1

'Dr. Kobilka is Professor of Medicine, Cardiology, and Molecular and Cellular Physiology at Stanford University School of Medicine. He received his undergraduate degree in biology and chemistry from the University of Minnesota, Duluth, and his M.D. degree from Yale University. After his residency in internal medicine at Barnes Hospital, St. Louis, he joined the laboratory of Robert Lefkowitz as a research fellow in cardiology at Duke University, where he was later Assistant Professor in the Department of Medicine before joining the faculty at Stanford.'2

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