TY - JOUR T1 - Understanding Molecular Recognition by G protein βγ Subunits on the Path to Pharmacological Targeting JF - Molecular Pharmacology JO - Mol Pharmacol SP - 551 LP - 557 DO - 10.1124/mol.111.073072 VL - 80 IS - 4 AU - Yuan Lin AU - Alan V. Smrcka Y1 - 2011/10/01 UR - http://molpharm.aspetjournals.org/content/80/4/551.abstract N2 - Heterotrimeric G proteins, composed of Gα and Gβγ subunits, transduce extracellular signals via G-protein-coupled receptors to modulate many important intracellular responses. The Gβγ subunits hold a central position in this signaling system and have been implicated in multiple aspects of physiology and the pathophysiology of disease. The Gβ subunit belongs to a large family of WD40 repeat proteins with a circular β-bladed propeller structure. This structure allows Gβγ to interact with a broad range of proteins to play diverse roles. How Gβγ interacts with and regulates such a wide variety of partners yet maintains specificity is an interesting problem in protein-protein molecular recognition in signal transduction, where signal transfer by proteins is often driven by modular conserved recognition motifs. Evidence has accumulated that one mechanism for Gβγ multitarget recognition is through an intrinsically flexible protein surface or “hot spot” that accommodates multiple modes of binding. Because each target has a unique recognition mode for Gβγ subunits, it suggests that these interactions could be selectively manipulated with small molecules, which could have significant therapeutic potential. ER -