Researchers from SciLifeLab and the Rockefeller University (New York) have presented a new method for studying the “interactome” of G protein-coupled receptors (GPCRs) and Receptor activity-modifying proteins (RAMPs).

GPCRs are a very important class of cell receptors involved in everything from vision and taste to hormonal regulation and neuronal communication. Intracellular signalling is activated by ligands binding to the external part of the receptor and for this reason they serve as excellent drug targets.

One challenge for drug discovery is that receptors are embedded into the cell surface membrane, and studying them is challenging. Another problem is that a number of drugs, successful in preclinical studies, have failed in human trials due to unknown reasons. Scientists have since discovered that many of the GPCRs interact with another group of proteins, so called RAMPs, that can bind to and change the structure of the receptor making it respond differently in vivo than in vitro.

In a recent study, led by Jochen Schwenk (SciLifeLab/KTH) and Thomas Sakmar (The Rockefeller University/KI), researchers developed a multiplexed assay that could detect a large number of GPCR-RAMP complexes simultaneously. In the study, published in Science Advances, the researchers used antibodies from the Human Protein Atlas and suspension bead arrays to map the interactions of 23 different GPCRs together with three known RAMPs.

“Antibodies are fantastic research tools but they have to be validated for the specific applications, so you need to carefully design the assay and adapt the conditions for each type of sample and its preparations to make the antibodies work at their best”, says Jochen Schwenk.

The study revealed previously reported GPCR-RAMP interactions but also identified many new ones, including some RAMP interaction with orphan receptors that have unknown natural ligands. The results also provided a complete interactome of secretin-like family of GPCRs and RAMPs.

“This project is a great example of what is possible when complementary expertise and engagement meet to push the limits of the current analytical capabilities.”, says Jochen Schwenk.

These insights could play an important role in drug discovery and help researchers understand a number of GPCR-linked diseases. Looking forward, the strategy could also be helpful when studying other interacting membrane protein pairs in both cell lines and tissues.

 

 

This website uses cookies to improve your experience. We'll assume you're ok with this, but you can opt-out if you wish. Ok!Read More
Privacy & Cookies Policy

Privacy Overview

This website uses cookies to improve your experience while you navigate through the website. Out of these cookies, the cookies that are categorized as necessary are stored on your browser as they are essential for the working of basic functionalities of the website. We also use third-party cookies that help us analyze and understand how you use this website. These cookies will be stored in your browser only with your consent. You also have the option to opt-out of these cookies. But opting out of some of these cookies may have an effect on your browsing experience.
Necessary
Always Enabled

Necessary cookies are absolutely essential for the website to function properly. This category only includes cookies that ensures basic functionalities and security features of the website. These cookies do not store any personal information.

Non-necessary

Any cookies that may not be particularly necessary for the website to function and is used specifically to collect user personal data via analytics, ads, other embedded contents are termed as non-necessary cookies. It is mandatory to procure user consent prior to running these cookies on your website.