Nanobodies: New avenues for imaging, stabilizing and modulating GPCRs

Research output: Contribution to JournalReview articleAcademicpeer-review

Abstract

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.

LanguageEnglish
Pages15-24
Number of pages10
JournalMolecular and Cellular Endocrinology
Volume484
DOIs
Publication statusPublished - 15 Mar 2019

Fingerprint

Single-Domain Antibodies
G-Protein-Coupled Receptors
Imaging techniques
Immunoglobulin Fragments
Antibodies
Physiological Phenomena
Molecules
Monomeric GTP-Binding Proteins
Conformations
Membrane Proteins
Stabilization

Keywords

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

Cite this

@article{40f8bba5f0324a48b1b508f68880a2a8,
title = "Nanobodies: New avenues for imaging, stabilizing and modulating GPCRs",
abstract = "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.",
keywords = "Antibodies, Crystallization, G protein-coupled receptors, Imaging, Modulation, Nanobodies",
author = "{De Groof}, {Timo W.M.} and Vladimir Bobkov and Raimond Heukers and Smit, {Martine J.}",
year = "2019",
month = "3",
day = "15",
doi = "10.1016/j.mce.2019.01.021",
language = "English",
volume = "484",
pages = "15--24",
journal = "Molecular and Cellular Endocrinology",
issn = "0303-7207",
publisher = "Elsevier Ireland Ltd",

}

Nanobodies : New avenues for imaging, stabilizing and modulating GPCRs. / De Groof, Timo W.M.; Bobkov, Vladimir; Heukers, Raimond; Smit, Martine J.

In: Molecular and Cellular Endocrinology, Vol. 484, 15.03.2019, p. 15-24.

Research output: Contribution to JournalReview articleAcademicpeer-review

TY - JOUR

T1 - Nanobodies

T2 - Molecular and Cellular Endocrinology

AU - De Groof, Timo W.M.

AU - Bobkov, Vladimir

AU - Heukers, Raimond

AU - Smit, Martine J.

PY - 2019/3/15

Y1 - 2019/3/15

N2 - 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.

AB - 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.

KW - Antibodies

KW - Crystallization

KW - G protein-coupled receptors

KW - Imaging

KW - Modulation

KW - Nanobodies

UR - http://www.scopus.com/inward/record.url?scp=85060749931&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85060749931&partnerID=8YFLogxK

U2 - 10.1016/j.mce.2019.01.021

DO - 10.1016/j.mce.2019.01.021

M3 - Review article

VL - 484

SP - 15

EP - 24

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

SN - 0303-7207

ER -