期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 484, 期 -, 页码 15-24出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2019.01.021
关键词
G protein-coupled receptors; Nanobodies; Antibodies; Imaging; Crystallization; Modulation
资金
- Netherlands Organization for Scientific Research (NWO VICI grant) [016.140.657]
- EU horizon's 2020 MSA programme [ONCORNET 641833]
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.
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