Receptor selectivity between the G proteins Gα12 and Gα13 is defined by a single leucine-to-isoleucine variation

What is it about?

G protein coupled receptors regulate almost every aspect of physiology. They do so because when they are bound by a hormone or neurotransmitter they activate one or more members of the G protein family. However, despite many years of study we have little insight into the features that result in activated G protein coupled receptors selecting one over other members of this family. Herein we explore the molecular details of a receptor called GPR35 does so. We show by combinations of molecular manipulation and computational analysis that selection of one closely related G protein over another can be defined by a single amino acid difference between them. This is unexpected but may allow the design of medicines that can improve such selection to enhance selectivity and reduce drug toxicity if we fully understand these rules of selection.

Featured Image