Nanobodies detecting and modulating GPCRs outside in and inside out

Area of Science:

• Biochemistry
• Molecular Biology
• Pharmacology

Background:

• G protein-coupled receptors (GPCRs) are a major class of membrane proteins involved in numerous physiological processes.
• GPCRs are significant drug targets, traditionally addressed by small molecules.
• Camelid-derived heavy chain-only antibodies (nanobodies) are emerging as novel tools for GPCR targeting.

Purpose of the Study:

• To review the current applications of nanobodies targeting GPCRs.
• To explore the potential of nanobodies for modulating GPCR activity.
• To discuss the use of nanobodies in GPCR structural biology and drug discovery.

Main Methods:

• Literature review of nanobody applications against GPCRs.
• Analysis of nanobody characteristics enabling GPCR interaction (size, structure).
• Discussion of nanobody functionalization for imaging and therapeutic purposes.

Main Results:

• Nanobodies can bind and modulate GPCRs from intracellular and extracellular sides due to their small size.
• Functionalized nanobodies serve as tools for GPCR imaging and therapy.
• GPCR-specific nanobodies have aided in obtaining crucial crystal structures for drug discovery.

Conclusions:

• Nanobodies represent versatile tools for studying, modulating, and targeting GPCRs.
• Their unique properties open new avenues for therapeutic interventions and structure-based drug design.
• Future perspectives involve expanded use of nanobodies in GPCR research and clinical applications.