This year’s Nobel Prize for Chemistry has been awarded to Robert J. Lefkowitz and Brian K. Kobilka for their studies of G-protein–coupled receptors.
G-protein–coupled receptors (GPCRs) are signalling proteins which enable cells to communicate with each other and the surrounding environment. They provide the molecular framework and mechanism for the transmission of a wide variety of signals over the cell membrane, between cells and over long distances in the body. GPCRs represent the largest family of membrane proteins in the human genome. They are remarkably versatile and are responsible for the majority of transmembrane signal transduction in response to hormones and neurotransmitters. GPCRs activate G proteins, which subsequently regulate downstream effector proteins.
The groundbreaking studies by Lefkowitz and Kobilka reveal the inner workings of this vitally important family of receptors. The crystal structures of the beta2 adrenergic receptor were determined using X-ray diffraction by Kobilka’s group. The structures 2rh1, 2r4r and 2r4s were published and released in 2007. Subsequently, the structure of a G protein (Gs) bound to the beta2 adrenergic receptor 3sn6 was determined using X-ray diffraction by the same group at a resolution of 3.2 Å and published in 2011, providing important insights into how GPCRs activate G proteins.
This year’s Nobel Prize is yet another example of the extraordinary contribution made by crystallographers and structural biologists to the fields of chemistry, biology and medicine. The Foundation has awarded more than 20 Nobel Prizes to structural biologists in the past 50 years. These include the Nobel Prize for Chemistry in 1962 (for studies of the structures of globular proteins) to John Kendrew and Max Perutz and the Nobel Prize in Physiology or Medicine in the same year to Francis Crick, James Watson and Maurice Wilkins (for their studies of “The helical structure of DNA”).
Outreach Coordinator Protein Data Bank in Europe (PDBe) EMBL-EBI