Nanobodies to Study G Protein–Coupled Receptor Structure and Function
| Autor: | Jan Steyaert, Aashish Manglik, Brian K. Kobilka |
|---|---|
| Přispěvatelé: | Structural Biology Brussels, Department of Bio-engineering Sciences |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Single-Domain Antibodies/chemistry Protein Conformation Protein Conformation/drug effects Isoproterenol/chemistry Ligands Toxicology Article Protein Structure Secondary Intrabody Receptors G-Protein-Coupled 03 medical and health sciences conformational plasticity Animals Humans G protein-coupled receptor Receptor Pharmacology Dose-Response Relationship Drug biology receptor activation Receptors G-Protein-Coupled/chemistry Isoproterenol Protein Binding/physiology Single-Domain Antibodies Transmembrane signaling Protein Structure Tertiary Cell biology Structure and function intrabody Important research 030104 developmental biology crystallographic chaperone Nanobody biology.protein Signal transduction hormones hormone substitutes and hormone antagonists Function (biology) Protein Binding |
| Zdroj: | Annual Review of Pharmacology and Toxicology. 57:19-37 |
| ISSN: | 1545-4304 0362-1642 |
| Popis: | 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 agonistbound 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. Expected final online publication date for the Annual Review of Pharmacology and Toxicology Volume 57 is January 06, 2017. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates. |
| Databáze: | OpenAIRE |
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