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Science 335 (6072): 1055-1056

Copyright © 2012 by the American Association for the Advancement of Science

Structural Origins of Receptor Bias

Stephen R. Sprang, and Jackson Chief Elk

Humans express more than 800 G protein–coupled receptors (GPCRs), through which myriad physiological, immune, and neurophysiological processes are regulated (1). These receptors are embedded in the cell's plasma membrane and bind to extracellular chemical stimuli (agonists). This interaction induces conformational changes in the receptor that converge at intracellular sites that bind to either heterotrimeric guanine nucleotide–binding proteins (G proteins) or to β-arrestin proteins that block G protein binding and lead to receptor desensitization and internalization, as well as provide a scaffold for protein regulatory complexes that control gene expression (2). Many agonists induce functionally selective or biased states of the receptor, wherein one pathway is activated with greater efficacy than another (3). Thus, GPCRs are not simple on-off switches, but can adopt multiple conformational states to control diverse processes. On page 1106 of this issue, Liu et al. (4) provide clues as to how a GPCR called the β2-adrenergic receptor (β2AR) can tune its conformation to achieve a balance of functional outcomes, as directed by the chemical structure of the receptor agonist.

Center for Biomolecular Structure and Dynamics, University of Montana, Missoula, MT 59812, USA.

E-mail: stephen.sprang{at}

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