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

14.05.2003


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).

Judith H Moore | alfa
Further information:
http://www.ic.ac.uk

More articles from Life Sciences:

nachricht Cells migrate collectively by intermittent bursts of activity
30.09.2016 | Aalto University

nachricht The structure of the BinAB toxin revealed: one small step for Man, a major problem for mosquitoes!
30.09.2016 | CNRS (Délégation Paris Michel-Ange)

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-Ever 3D Printed Excavator Project Advances Large-Scale Additive Manufacturing R&D

Heavy construction machinery is the focus of Oak Ridge National Laboratory’s latest advance in additive manufacturing research. With industry partners and university students, ORNL researchers are designing and producing the world’s first 3D printed excavator, a prototype that will leverage large-scale AM technologies and explore the feasibility of printing with metal alloys.

Increasing the size and speed of metal-based 3D printing techniques, using low-cost alloys like steel and aluminum, could create new industrial applications...

Im Focus: New welding process joins dissimilar sheets better

Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of light metals.
Scientists at the University of Stuttgart have now developed two new process variants that will considerably expand the areas of application for friction stir welding.
Technologie-Lizenz-Büro (TLB) GmbH supports the University of Stuttgart in patenting and marketing its innovations.

Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of...

Im Focus: First quantum photonic circuit with electrically driven light source

Optical quantum computers can revolutionize computer technology. A team of researchers led by scientists from Münster University and KIT now succeeded in putting a quantum optical experimental set-up onto a chip. In doing so, they have met one of the requirements for making it possible to use photonic circuits for optical quantum computers.

Optical quantum computers are what people are pinning their hopes on for tomorrow’s computer technology – whether for tap-proof data encryption, ultrafast...

Im Focus: OLED microdisplays in data glasses for improved human-machine interaction

The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.

“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...

Im Focus: Artificial Intelligence Helps in the Discovery of New Materials

With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.

Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Paper – Panacea Green Infrastructure?

30.09.2016 | Event News

HLF: From an experiment to an establishment

29.09.2016 | Event News

European Health Forum Gastein 2016 kicks off today

28.09.2016 | Event News

 
Latest News

First-Ever 3D Printed Excavator Project Advances Large-Scale Additive Manufacturing R&D

30.09.2016 | Materials Sciences

New Technique for Finding Weakness in Earth’s Crust

30.09.2016 | Earth Sciences

Cells migrate collectively by intermittent bursts of activity

30.09.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>