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 communicate in a dynamic code
19.02.2018 | California Institute of Technology

nachricht Studying mitosis' structure to understand the inside of cancer cells
19.02.2018 | Biophysical Society

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Contacting the molecular world through graphene nanoribbons

19.02.2018 | Materials Sciences

When Proteins Shake Hands

19.02.2018 | Materials Sciences

Cells communicate in a dynamic code

19.02.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>