Nanobodies: New avenues for imaging, stabilizing and modulating GPCRs

Timo W.M. De Groof, Vladimir Bobkov, Raimond Heukers, Martine J. Smit*

*Corresponding author for this work

Research output: Contribution to JournalReview articleAcademicpeer-review


The family of G protein-coupled receptors (GPCRs) is the largest class of membrane proteins and an important drug target due to their role in many (patho)physiological processes. Besides small molecules, GPCRs can be targeted by biologicals including antibodies and antibody fragments. This review describes the use of antibodies and in particular antibody fragments from camelid-derived heavy chain-only antibodies (nanobodies/VHHs/sdAbs) for detecting, stabilizing, modulating and therapeutically targeting GPCRs. Altogether, it becomes increasingly clear that the small size, structure and protruding antigen-binding loops of nanobodies are favorable features for the development of selective and potent GPCRs-binding molecules. This makes them attractive tools to modulate GPCR activity but also as targeting modalities for GPCR-directed therapeutics. In addition, these antibody-fragments are important tools in the stabilization of particular conformations of these receptors. Lastly, nanobodies, in contrast to conventional antibodies, can also easily be expressed intracellularly which render nanobodies important tools for studying GPCR function. Hence, GPCR-targeting nanobodies are ideal modalities to image, stabilize and modulate GPCR function.

Original languageEnglish
Pages (from-to)15-24
Number of pages10
JournalMolecular and Cellular Endocrinology
Publication statusPublished - 15 Mar 2019


This work was supported by The Netherlands Organization for Scientific Research (NWO VICI grant 016.140.657 ); EU horizon’s 2020 MSA programme (ONCORNET 641833 ).

FundersFunder number
EU horizon's 2020 MSA
EU horizon’s 2020 MSAONCORNET 641833
Netherlands Organization for Scientific Research
Horizon 2020 Framework Programme641833
Nederlandse Organisatie voor Wetenschappelijk Onderzoek016.140.657


    • Antibodies
    • Crystallization
    • G protein-coupled receptors
    • Imaging
    • Modulation
    • Nanobodies


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