Nanobodies detecting and modulating GPCRs outside in and inside out

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

Research output: Contribution to JournalReview articleAcademicpeer-review


G protein-coupled receptors (GPCRs), belonging to the largest class of membrane proteins, play a prominent role in many (patho)physiological processes and are, therefore, important drug targets. Although most often targeted by small molecules, these receptors have become interesting targets for antibodies and antibody fragments, especially camelid-derived heavy chain-only antibodies and fragments thereof (nanobodies). The small size and molecular structure of nanobodies allow GPCR-binding and modulation, from both the intracellular and extracellular sides. These molecular features make nanobodies attractive tools to study, modulate, and exploit GPCRs. Besides modulating GPCR activity as monovalent or multivalent constructs, nanobodies can also be functionalized for imaging and therapy. Moreover, GPCR-binding nanobodies have been instrumental in obtaining crystal structures of GPCRs, facilitating structure-based drug discovery. Here, we describe the current status and future perspectives of nanobodies targeting GPCRs intra and extracellularly.

Original languageEnglish
Pages (from-to)115-122
Number of pages8
JournalCurrent Opinion in Cell Biology
Publication statusPublished - 1 Apr 2019


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