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Profile of Brian K. Kobilka and Robert J. Lefkowitz, 2012 Nobel Laureates in Chemistry

2013; National Academy of Sciences; Volume: 110; Issue: 14 Linguagem: Inglês

10.1073/pnas.1221820110

1091-6490

Richard B. Clark,

Protein Kinase Regulation and GTPase Signaling

Those of us that had been hammering away in the field for 40 years or more cannot deny the excitement in learning that Brian Kobilka, a former postdoctoral fellow of Robert Lefkowitz, in collaboration with Roger Sunahara, had determined the structure of the agonist-bound β2-adrenergic receptor-Gs protein complex (1). To borrow a phrase from Henry Bourne, this is “the Big Enchilada” for the G protein-coupled receptor (GPCR)/G protein field. This work followed just five years after Kobilka and Schertler’s determination of the crystal structure of the β2-adrenergic receptor (β2AR) bound to the inverse agonist carazolol (2), and over two and a half decades after the reports by Robert Lefkowitz’s group of the purification, cloning, and sequencing of the mammalian β2AR (3, 4). These remarkable achievements and others discussed below led to the award of the 2012 Nobel Prize in Chemistry to Kobilka and Lefkowitz. This was another big win for GPCRs, G proteins, and second messengers, a field that has already been richly rewarded, and justifiably so, for the role they play in hormone and neurotransmitter signaling and pharmacology.