Nanobody stabilization of G protein-coupled receptor conformational states.

TitleNanobody stabilization of G protein-coupled receptor conformational states.
Publication TypeJournal Article
Year of Publication2011
AuthorsSteyaert, J., and B. K. Kobilka
JournalCurr Opin Struct Biol
Volume21
Issue4
Pagination567-72
Date Published2011 Aug
ISSN1879-033X
KeywordsAnimals, Crystallography, X-Ray, Humans, Immunoglobulin Fragments, Protein Conformation, Protein Stability, Receptors, G-Protein-Coupled, Single-Chain Antibodies
Abstract

Remarkable progress has been made in the field of G protein-coupled receptor (GPCR) structural biology during the past four years. Several obstacles to generating diffraction quality crystals of GPCRs have been overcome by combining innovative methods ranging from protein engineering to lipid-based screens and microdiffraction technology. The initial GPCR structures represent energetically stable inactive-state conformations. However, GPCRs signal through different G protein isoforms or G protein-independent effectors upon ligand binding suggesting the existence of multiple ligand-specific active states. These active-state conformations are unstable in the absence of specific cytosolic signaling partners representing new challenges for structural biology. Camelid single chain antibody fragments (nanobodies) show promise for stabilizing active GPCR conformations and as chaperones for crystallogenesis.

DOI10.1016/j.sbi.2011.06.011
Alternate JournalCurr. Opin. Struct. Biol.
PubMed ID21782416
PubMed Central IDPMC3166880
Grant ListGM083118 / GM / NIGMS NIH HHS / United States
NS028471 / NS / NINDS NIH HHS / United States
R01 GM083118 / GM / NIGMS NIH HHS / United States
R01 GM083118-03 / GM / NIGMS NIH HHS / United States
R01 GM083118-04 / GM / NIGMS NIH HHS / United States
R37 NS028471 / NS / NINDS NIH HHS / United States
R37 NS028471-20 / NS / NINDS NIH HHS / United States