Advances in the Study of Structure and Function of G Protein-Coupled Receptors (About Awarding the Nobel Prize for Chemistry in 2012 to Robert Leikowitz and Brian Kobilka)

摘要

The 2012 Nobel Prize for Chemistry was awarded to Robert Lefkowitz and Brian Kobilka "for study in G-protein-coupled receptors" (GPCR). In this review there are discussed and analyzed the most important discoveries of these Nobel Laureates dealing with study of structure and functions of GPCR. In the 1980s they were the first in the world to clone GPCR—the β2-adrenergic receptor. After 20 years the group headed by B. Kobilka first obtained this receptor in the crystallic form and established its three-dimensional structure. In the course of the studies, unique approaches were developed for purifications and crystallization of other receptors. In the 1980s, R. Lefkowitz and his colleagues discovered proteins β-arrestins that regulate the signal transduction realized via GPCR. Subsequently they showed β-arrestins to be the most important participants of signal transduction and to be responsible for transduction of signal from the receptor activated with hormone to intracellular signal cascades regardless of heterotrimeric G-proteins. These and other outstanding discoveries of R. Lefkowitz and B. Kobilka have become the ground of the new field of molecular biology and pharmacology—molecular endocrinology of GPCR.