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Annu Rev Pharmacol Toxicol. 2017 Jan 6;57:19-37. doi: 10.1146/annurev-pharmtox-010716-104710. Epub 2016 Dec 7.

Nanobodies to Study G Protein-Coupled Receptor Structure and Function.

Author information

1
Department of Molecular and Cellular Physiology, Stanford University, Stanford, California 94305; email: amanglik@stanford.edu , kobilka@stanford.edu.
2
Structural Biology Brussels, Vrije Universiteit Brussel, 1050 Brussels, Belgium; email: jan.steyaert@vub.ac.be.
3
VIB Structural Biology Research Center, Vrije Universiteit Brussel, 1050 Brussels, Belgium.

Abstract

Ligand-induced activation of G protein-coupled receptors (GPCRs) is a key mechanism permitting communication between cells and organs. Enormous progress has recently elucidated the structural and dynamic features of GPCR transmembrane signaling. Nanobodies, the recombinant antigen-binding fragments of camelid heavy-chain-only antibodies, have emerged as important research tools to lock GPCRs in particular conformational states. Active-state stabilizing nanobodies have elucidated several agonist-bound structures of hormone-activated GPCRs and have provided insight into the dynamic character of receptors. Nanobodies have also been used to stabilize transient GPCR transmembrane signaling complexes, yielding the first structural insights into GPCR signal transduction across the cellular membrane. Beyond their in vitro uses, nanobodies have served as conformational biosensors in living systems and have provided novel ways to modulate GPCR function. Here, we highlight several examples of how nanobodies have enabled the study of GPCR function and give insights into potential future uses of these important tools.

KEYWORDS:

G protein–coupled receptor; conformational plasticity; crystallographic chaperone; intrabody; nanobody; receptor activation

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