Nanobody stabilization of G protein-coupled receptor conformational states

Jan Steyaert, Brian K. Kobilka

Research output: Contribution to journalReview ArticleResearchpeer-review

168 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)567-572
Number of pages6
JournalCurrent Opinion in Structural Biology
Volume21
Issue number4
DOIs
Publication statusPublished - Aug 2011
Externally publishedYes

Cite this