Understanding molecular recognition by G protein ?? subunits on the path to pharmacological targeting.

ABSTRACT: Heterotrimeric G proteins, composed of G? and G?? subunits, transduce extracellular signals via G-protein-coupled receptors to modulate many important intracellular responses. The G?? subunits hold a central position in this signaling system and have been implicated in multiple aspects of physiology and the pathophysiology of disease. The G? subunit belongs to a large family of WD40 repeat proteins with a circular ?-bladed propeller structure. This structure allows G?? to interact with a broad range of proteins to play diverse roles. How G?? 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 G?? 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 G?? subunits, it suggests that these interactions could be selectively manipulated with small molecules, which could have significant therapeutic potential.

SUBMITTER: Lin Y 

PROVIDER: S-EPMC3187535 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature