Corporate Banner
Satellite Banner
Crystallography
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Discovery of New Structure of Cell’s Communication Channel Could Aid Drug Development

Published: Wednesday, April 30, 2014
Last Updated: Wednesday, April 30, 2014
Bookmark and Share
Researchers hope discovery will lead to improvements in drugs that act on the sodium channel to treat a range of cardiac and pain conditions.

The structure of sodium channels – which play an essential role in the functioning of heart and nerve cells – are different than previously believed. 

Sodium channels are implicated in many serious conditions such as heart disease, epilepsy and pain, making them an important potential target for drug therapies. Unfortunately, there is still much scientists do not know about the molecules. New Cambridge research provides fresh and unexpected insight into the structure of sodium channels and, specifically, one of its components - β-subunit molecules - which are responsible for ‘fine-tuning’ the activity of the channel. The research is published in the most recent edition of the Journal of Biological Chemistry.

Nerves and other electrically-excitable cells communicate with one another by transmitting electrical signals, and sodium channels play a vital role in this process. The sodium channel lies on the surface of the nerve and muscle cells and is composed of a large molecule called the α-subunit, together with smaller β-subunit molecules. The b-subunits ‘fine-tune’ the activity of the channel, so that the initiation, frequency and duration of the action potential can be appropriately regulated. There are ten different forms of α-subunits and four different forms of b-subunits. These are expressed in different types of cells and organs within the body.

The new Cambridge research was carried out by Sivakumar Namadurai and led by Dr Tony Jackson and Dr Dima Chirgadze from the University of Cambridge’s Department of Biochemistry, and focussed on one of the b-subunits, called β3. This molecule is particularly important in regulating sodium channels located on heart cells.

For the study, the researchers used a technique called protein X-ray crystallography to determine the atomic-resolution structure of a part of the b3-subunit called the ‘immunoglobulin domain’. This region of the b3-subunit lies on the outside of the cell and binds to the heart sodium channel α-subunit.

They discovered that three b3-immunoglobulin domains come together to form a trimer (so-called because it is made up of three molecules). Using a technique called atomic force microscopy, Dilshan Balasuriya, led by Professor Mike Edwardson in Cambridge’s Department of Pharmacology, imaged individual b3 trimers and confirmed that the complete b3-subunit trimers cross-linked up to three sodium channel α-subunits.

“Our results were unexpected,” said Dr Jackson. “We have been working on the b3-subunit for about 14 years. In all that time, we have had to infer events at the molecular level indirectly. To actually see the atomic structure of the subunit and how it forms the trimer was one of those rare ‘a-ha!’ moments, like switching on a light bulb.”

Dr Chirgadze added: “Our research has important implications for our understanding of the mechanism of sodium channel behaviour. Up until now there has been an assumption that individual sodium channels function independently. But this might be too simple a view. One very exciting possibility is that the cross-linking of sodium channel α-subunits by b3 trimers could lead to several sodium channels being functionally connected together. If correct, this would allow a more efficient initiation of the action potential.”


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,900+ scientific posters on ePosters
  • More than 4,200+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.


Scientific News
Crouching Protein, Hidden Enzyme
A new study led by scientists at The Scripps Research Institute (TSRI) and the University of California (UC), Berkeley shows how a crucial molecular enzyme starts in a tucked-in somersault position and flips out when it encounters the right target.
Spotlight on Acoustic Liquid Handling
Journal of Laboratory Automation special issue highlights how acoustic liquid handling enables breakthrough innovations.
3D Images of Enzymes May Lead to Improved Antibiotics
Research advances understanding of how crucial proteins function.
Supply Chain
Chemists discover how a single enzyme maintains a cell’s pool of DNA building blocks.
Seeing DROSHA for the First Time
IBS team gets the first glimpse of elusive protein structure.
Scientists Blueprint Tiny Cellular ‘Nanomachine’
Scientists have drawn up molecular blueprints of a tiny cellular ‘nanomachine’, whose evolution is an extraordinary feat of nature, by using one of the brightest X-ray sources on Earth.
Pioneering Brain Cancer Technique Could Lead to Better Prognosis for Patients
4,000th paper published from Diamond research could improve outcomes for brain cancer sufferers.
Big Moves in Protein Structure Prediction and Design
Custom design with atomic level accuracy enables researchers to craft a whole new world of proteins.
Pushing Drug Discovery Forward
A new study, led by scientists at The Scripps Research Institute (TSRI), shows how different pharmaceutical drugs hit either the “on” or “off” switch of a signaling protein linked to asthma, obesity and type 2 diabetes.
Solved Structure of S. pneumoniae Enzyme Could Lead to New Antibiotics
Scientists solve structure of a key bacterial enzyme from streptococcus pneumoniae: a major cause of bacterial meningitis, bronchitis, ear infection and pneumonia.
SELECTBIO

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,900+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,200+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!