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 Transport of molecular motors into cilia
28.03.2017 | Aarhus University

nachricht Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Transport of molecular motors into cilia

28.03.2017 | Life Sciences

A novel hybrid UAV that may change the way people operate drones

28.03.2017 | Information Technology

NASA spacecraft investigate clues in radiation belts

28.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>