Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study of thyroxine transporter molecule shows how key hormone hitches a lift round body

15.05.2003


Findings may aid the development of drugs to treat thyroid disorders



Structural analysis has revealed for the first time how a key messenger in the body’s chemical communication system hooks up with one of the proteins that delivers it to sites of action in the body.

Using X-ray crystallography, scientists from Imperial College London and the University of Hawaii have identified the location of four binding sites on human serum albumin (HSA), the principal protein in blood plasma, to which the chemical messenger thyroxine attaches.


Thyroxine is the primary hormone released from the thyroid gland, and acts on nearly every cell in the body affecting important mechanisms that control, weight, energy level, memory and heart rate.

While HSA is not the major transporter of thyroxine, its quick and direct action provides the most ready supply of the hormone for use around the body.

The findings, which are published online this week in the Proceedings of the National Academy of Science, help to explain how thyroxine regulates metabolic processes and normal physical development, and may aid the development of drugs to treat thyroid disorders.

The structural information also sheds light on the molecular basis of a rare condition, familial dysalbuminemic hyperthyroxemia (FDH), which is caused by mutations in HSA. This harmless genetic disorder is often misdiagnosed as an overactive thyroid gland and treated inappropriately.

Dr Stephen Curry of Imperial’s Department of Biological Sciences and senior author of the study said:

"Our study provides a more complete understanding of how thyroxine binds to HSA. Previously the number and location of binding sites on HSA was not clear. This structural information can now be used to help design synthetic forms of thyroxine to treat thyroid disorders. It will allow more detailed analysis of how the two molecules interact in the body, which can be used to make more effective candidate drugs."

HSA is the most abundant protein in the circulatory system. Its principal function is to transport fatty acids, but it is also one of three proteins that delivers thyroxine.

Levels of thyroxine circulating in the body are used as a biochemical indicator to help gauge how active the thyroid gland is. The researchers sought a better understanding of how the hormone binds to the proteins that transport it in order to improve diagnosis of the various thyroid disorders.

Together with colleagues in Hawaii, the Imperial team, who are the main academic research group in the world working on albumin structures, examined the crystallised structure of HSA bound to thyroxine under three different conditions: in the presence or absence of fatty acids and using mutant forms of HSA.

"The shape of the HSA-thyroxine complex alters dramatically when fatty acids bind to the protein," explained Dr Curry. "The main difference is that when fatty acids are present, their binding creates a new binding site.

"This is an unprecedented example of the complex interplay between the binding of fatty acids and thyroxine to the protein. Although fatty acids and thyroxine compete with one another to bind to several sites on the protein, there is also an element of cooperation through the creation of an additional binding site for the hormone. "The interaction between the FDH causing mutant forms of HSA and thyroxine increases the binding affinity between the two molecules 10 to 15 fold. People with this condition present with normal levels of thyroxine that is not bound to transporter proteins but when the total level of thyroxine is looked at it’s much higher. Our research will allow a more accurate diagnosis of this condition in the future."

The research was supported by the American Heart Foundation, Hawaii Affiliate and the Biotechnology and Biological Sciences Research Council (UK).


For further information, please contact:

Judith H Moore
Imperial College London Press Office
Tel: 44-207-594-6702
Mobile: 44-780-388-6248
E-mail: j.h.moore@imperial.ac.uk

Judith H Moore | EurekAlert!
Further information:
http://www.ic.ac.uk/
http://www.imperial.ac.uk

More articles from Life Sciences:

nachricht New eDNA technology used to quickly assess coral reefs
18.04.2019 | University of Hawaii at Manoa

nachricht New automated biological-sample analysis systems to accelerate disease detection
18.04.2019 | Polytechnique Montréal

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Explosion on Jupiter-sized star 10 times more powerful than ever seen on our sun

A stellar flare 10 times more powerful than anything seen on our sun has burst from an ultracool star almost the same size as Jupiter

  • Coolest and smallest star to produce a superflare found
  • Star is a tenth of the radius of our Sun
  • Researchers led by University of Warwick could only see...

Im Focus: Quantum simulation more stable than expected

A localization phenomenon boosts the accuracy of solving quantum many-body problems with quantum computers which are otherwise challenging for conventional computers. This brings such digital quantum simulation within reach on quantum devices available today.

Quantum computers promise to solve certain computational problems exponentially faster than any classical machine. “A particularly promising application is the...

Im Focus: Largest, fastest array of microscopic 'traffic cops' for optical communications

The technology could revolutionize how information travels through data centers and artificial intelligence networks

Engineers at the University of California, Berkeley have built a new photonic switch that can control the direction of light passing through optical fibers...

Im Focus: A long-distance relationship in femtoseconds

Physicists observe how electron-hole pairs drift apart at ultrafast speed, but still remain strongly bound.

Modern electronics relies on ultrafast charge motion on ever shorter length scales. Physicists from Regensburg and Gothenburg have now succeeded in resolving a...

Im Focus: Researchers 3D print metamaterials with novel optical properties

Engineers create novel optical devices, including a moth eye-inspired omnidirectional microwave antenna

A team of engineers at Tufts University has developed a series of 3D printed metamaterials with unique microwave or optical properties that go beyond what is...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

Fraunhofer FHR at the IEEE Radar Conference 2019 in Boston, USA

09.04.2019 | Event News

 
Latest News

New automated biological-sample analysis systems to accelerate disease detection

18.04.2019 | Life Sciences

Explosion on Jupiter-sized star 10 times more powerful than ever seen on our sun

18.04.2019 | Physics and Astronomy

New eDNA technology used to quickly assess coral reefs

18.04.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>