GPCRs for Drug Discovery and Development

About GPCRs

G protein-coupled receptors (GPCRs), also known as G-protein linked receptors, serpentine receptors, or heptahelical receptors, represent the largest superfamily of membrane proteins in the human genome. These integral membrane proteins possess seven membrane-spanning helices and function to transduce a diverse array of extracellular stimuli, including biogenic amines, peptides, hormones, neurotransmitters, ions, odorants, and photons, into intracellular signals. This transduction is facilitated by a ligand-induced conformational change in the GPCRs, which activates heterotrimeric G proteins (guanine nucleotide-binding proteins) essential for conveying the extracellular ligand signal to the cell's interior. G-proteins can be categorized based on homologous structure and common ligand subtypes. The regulatory impact of GPCRs spans physiological processes such as cell metabolism, differentiation, growth, neurotransmission, and sensory perception. Additionally, they are implicated in numerous diseases, including type 2 diabetes mellitus, obesity, depression, cancer, Alzheimer’s disease, and more, making them a prime drug target for various therapeutic interventions.

Challenges of Recombinant GPCR Expression

Extraction and purification of membrane proteins like GPCRs, ion channels, transporters are generally challenging due to low expression levels and hydrophobic nature of transmembrane segments. To tackle this challenge, KACTUS has engineered and produced GPCRs in VLP and /or nanodisc formats, which have been successfully applied to GPCR antibody drug discovery and various in vitro assays.

GPCR Nanodiscs

Nanodiscs has emerged as a powerful tool in functional and structural studies of GPCR. Membrane scaffold protein, Salipros, copolymer nanodiscs, which are different approaches of membrane protein extraction and assembly, have been developed. For instance, copolymer nanodiscs can incorporate GPCRs in their endogenous lipids via extracting the GPCR directly from the cell membranes. The assembled GPCR nanodiscs are soluble in aqueous media in a native-like bilayer environment that maintain GPCR's activity. GPCR nanodiscs are valuable in many biotechnological applications, especially in antibody drug discovery.

GPCR VLPs

Virus-like particles (VLPs) are non-infectious particles that mimic the structure of viruses but do not contain genetic material. They are often used in antibody drug discovery and as a tool for studying antigens including GPCRs. VLPs can be engineered to display specific GPCRs on their surface, making them useful for stimulating an immune response against particular GPCRs.

The process of displaying GPCRs on VLPs involves protein engineering techniques. The genes encoding the desired antigens are co-expressed with or inserted into the VLP-forming genes in bacteria or mammalian cells. As the organism produces VLPs, the GPCRs are incorporated into the VLPs' surface proteins. The displayed GPCRs are recognized by immune cells, such as B cells, which can produce antibodies specific to GPCRs.

Interested in learning more? Download the Poster!

Click here to download: GPCR VLPs and Nanodiscs for Drug Discovery

Nanodisc Ordering

Contact sales@kactusbio.us to request a GPCR nanodisc.