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 Single-stranded DNA and RNA origami go live
15.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

nachricht New antbird species discovered in Peru by LSU ornithologists
15.12.2017 | Louisiana State University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First-of-its-kind chemical oscillator offers new level of molecular control

DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.

Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Engineers program tiny robots to move, think like insects

15.12.2017 | Power and Electrical Engineering

One in 5 materials chemistry papers may be wrong, study suggests

15.12.2017 | Materials Sciences

New antbird species discovered in Peru by LSU ornithologists

15.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>