Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Molecular match-making: decoding ligand-receptor biochemistry

17.07.2015

Drugs like antihistamines or beta-blockers in human bodies bind to G-protein coupled receptors. Tiny little molecules that exist on the surface of our cells relay a signal from the outside to the inside of the cell, which finally evokes a reaction within. Humans have several hundred different receptors, many of which are vital for the functioning of their bodies.

Dr. Gáspár Jékely, independent research group leader at the Max Planck Institute for Developmental Biology in Tübingen, describes a new strategy to rapidly identify currently unknown receptors in the magazine Cell Report. Thereby his research group also sheds light on the evolutionary history of this widespread family of receptors.


Marine ragworm Platynereis dumerilii

Tom Pingel

With several hundred G-protein coupled receptors, so-called GPCRs, and many thousand potential ligands to test, it is difficult and time-consuming to find the right receptor-ligand combinations. The study focused on 87 Platynereis GPCRs and 126 different ligands, belonging to a specific class - the neuropeptides. With such large numbers of molecules, there were over 10,000 combinations to test.

“We had to come up with a clever strategy to get the work done in about a year rather than five years or more”, says Philipp Bauknecht, the PhD student who carried out the experiments. Much like in speed dating, every receptor should “meet” every neuropeptide in a very short amount of time. This was achieved by testing complex neuropeptide mixtures on each GPCR. A fluorescent protein would then report by emitting green light if there was a “match” between the GPCR and any of the ligands.

The researchers then continued only with the GPCRs that showed evidence of activation and tested combinations of mixtures containing only subsets of the neuropeptides. Combining the results from different mixtures allowed them to find the correct ligands for the GPCRs.

The GPCRs for which ligands had been identified were then used for evolutionary analysis. The researchers found related GPCRs from animals such as mollusks and insects, but also rats, mice and humans. For some of the GPCR families that were identified, this was the first example of what kind of ligand could activate them.

The team could show that some of the GPCR-ligand pairs are conserved across mammals, fish, insects and worms. These GPCR-ligand pairs were thus already present in the last common ancestor of ourselves and the ragworm Platynereis, an animal that lived about 550 million years ago.

A particularly interesting finding was the identification of a ligand for the invertebrate thyrotropin-releasing hormone receptor. As its name implies, the ligand for this receptor is the peptide thyrotropin-releasing hormone (TRH). This peptide occurs in vertebrates, where it functions in the control of metabolism. Invertebrates, however, were previously thought to lack this peptide while still having the receptor.

Through this study, the research group has identified a ligand for the invertebrate TRH receptor - a short neuropeptide that indeed seems to be related to vertebrate TRH. It was previously not recognized because it is so short and the few amino acids it is made up of changed during evolution. "Without having the receptor-ligand pair, we could not have solved this riddle", says Dr. Gáspár Jékely. The receptor is much longer, and conserved enough to show the relationships between vertebrate and invertebrate versions.

This new collection of GPCR-ligand pairs in the worm Platynereis will help other researchers in the field to identify similar pairs in other animals more easily. Furthermore, the strategy of using complex ligand mixtures is easily transferable to other species. Similar screens performed in other species could broaden our perspective of GPCR evolution even more.

Original Publication:
Philipp Bauknecht and Gáspár Jékely
Large-scale combinatorial deorphanization of Platynereis neuropeptide GPCRs, Cell Reports 2015
DOI:http://dx.doi.org/10.1016/j.celrep.2015.06.052

Weitere Informationen:

http://dx.doi.org/10.1016/j.celrep.2015.06.052

Nadja Winter | Max-Planck-Institut für Entwicklungsbiologie
Further information:
http://eb.mpg.de

Further reports about: GPCR GPCRs Max-Planck-Institut Molecular Platynereis animals hormone ligands receptor species vertebrate

More articles from Life Sciences:

nachricht New photocatalyst speeds up the conversion of carbon dioxide into chemical resources
29.05.2017 | DGIST (Daegu Gyeongbuk Institute of Science and Technology)

nachricht Copper hydroxide nanoparticles provide protection against toxic oxygen radicals in cigarette smoke
29.05.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Strathclyde-led research develops world's highest gain high-power laser amplifier

The world's highest gain high power laser amplifier - by many orders of magnitude - has been developed in research led at the University of Strathclyde.

The researchers demonstrated the feasibility of using plasma to amplify short laser pulses of picojoule-level energy up to 100 millijoules, which is a 'gain'...

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

New insights into the ancestors of all complex life

29.05.2017 | Earth Sciences

New photocatalyst speeds up the conversion of carbon dioxide into chemical resources

29.05.2017 | Life Sciences

NASA's SDO sees partial eclipse in space

29.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>