Navigation Links
Structure of Iron Regulatory Protein-RNA Complex Solved

The surprising structure and properties of a protein responsible for regulating the transport, storage and use of iron -- as it binds its target RNA// -- are described by researchers from the University of Illinois at Chicago.

Iron is an essential nutrient, and defects in uptake and metabolism that result in either deficiencies or overload of iron cause a variety of diseases and disorders, including heart disease, arthritis and cancer.

The iron regulating protein, called IRP1, has two structural forms, each with important functions within the cell.

When serving as one of two regulators of cellular iron metabolism through its control of gene expression, the tightly coiled IRP1 opens up to expose sites that bind messenger RNA at sites on the RNA called iron responsive elements, or IREs, that are common in genes involved in iron metabolism.

In its alternate form, IRP1 binds a cluster of iron and sulfur atoms to act as an important metabolic enzyme called aconitase. The assembly and disassembly of the iron/sulfur cluster in the aconitase form appears to be an effective mechanism for regulating IRP1 activity.

"We found that when IRP1 releases the iron/sulfur cluster and opens up to bind RNA, it undergoes an extraordinary, unexpected rearrangement," said William Walden, professor of microbiology and immunology at UIC and lead author of the study.

"This is the crucial step in understanding the specialized cellular processes that have evolved to maintain internal iron concentrations at the appropriate safe and useful levels and is important to the future design of therapeutic targets," Walden said.

IRP1 is a very large protein, composed of about 900 amino acids arranged into four major domains.

"We expected that IRP1 would open up the two major domains facing each other along a hinge, rather like a clam shell, to accommodate the RNA binding," Walden said. "What we didn't expect was that that opening up would also involve extensive movement within the domains."

The researchers also found two widely separated contact sites between IRP1 and the iron responsive element, said Karl Volz, associate professor in of microbiology and immunology at UIC and principle investigator of the study.

"This is one of the highest affinity bindings we have ever seen. The effect of binding a single iron responsive element, through interactions at two separate binding sites, essentially eliminates the possibility of non-specific binding," Volz said.

According to coauthor Elizabeth Theil, senior scientist at the Children's Hospital Oakland Research Institute in Oakland, Calif., just as drugs targeted to the three-dimensional protein structure emerged in the last century, "knowing how the iron response element RNA is folded in the IRP1 complex is a gift to drug design targeted to 3-D RNA structure -- a developing goal in this century."

The researchers believe the details of the IRP1:IRE interaction are likely also to apply to the other important iron regulatory molecule, IRP2, they wrote in their conclusion. "What remains to be determined is the evolutionary origin and selective advantage of such dramatic conformational plasticity and dual functionality as found in IRP1."

Source-Newswise
'"/>




Related medicine news :

1. Relationship Between Genetic Structure And Quality of Life
2. Abnormal Brain Structure One Of The Reasons For Depression in Adolescents
3. Structure of the brain to increase risk for anxiety disorders
4. Changes In Brain Structure From Methamphetamine Abuse And HIV Infection
5. Almond Structure in the Brain Intrigues Researchers
6. Controversy over Fees Structure in Private Medical Colleges
7. Controversy Over The Fee Structure In Private Medical Colleges Surfaces Yet Again
8. Education Structure In Indian Schools To Be Revamped Soon
9. Neither Management Nor Students Happy With New Fee Structure
10. DNA-bound p53 Tumor Suppressor Protein Structure Determined
11. Structure of DNA-modifying enzyme In Small Pox Determined
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:12/2/2016)... ... 2016 , ... Center for Autism and Related Disorders (CARD) Portland today announced ... disorder (ASD) and other developmental disabilities. The group, which is being launched with the ... the opportunity to share stories and advice, seek help, and continue their education on ...
(Date:12/2/2016)... ... 2016 , ... U.S. Surgeon General, Dr. Vivek Murthy, graces the cover of ... was inspired to practice medicine at an early age by his father, who was ... diagnoses and prescribing medicine,” he states. “It is about building relationships with people; relationships ...
(Date:12/2/2016)... ... December 02, 2016 , ... ... two ostomy patients, standing as living proof that attitude and determination can combine ... and issues that spike around the holidays. This campaign will offer patients a ...
(Date:12/2/2016)... ... December 02, 2016 , ... More than half of American teens report losing ... report speaking with their child about sex related topics, less than 60 percent spoke ... proud to announce the launch of its second edition of the “Sexual Wellness” campaign, ...
(Date:12/2/2016)... ... 02, 2016 , ... CloudLIMS.com, a class-leading provider of Laboratory ... CloudLIMS Lite helps biobanks, clinical, research and testing laboratories keep track of their ... version is a faster and a more efficient product, allowing batch processing of ...
Breaking Medicine News(10 mins):
(Date:12/2/2016)... -- UCB is pleased to announce that 12 scientific abstracts have ... American Epilepsy Society (AES) Annual Meeting, which takes place ... USA. 1-12 Data being presented include ... ® (lacosamide) CV and BRIVIACT ® (brivaracetam) CV. ... state of the union of epilepsy care and antiepileptic drugs ...
(Date:12/2/2016)... -- Allergan plc (NYSE: AGN ), a leading ... announced Accelerated Share Repurchase (ASR) Program. Logo - ... , ... announced, the Company entered into a variable tenor ASR arrangement ... $10 billion of its ordinary shares. Approximately 40.5 million shares ...
(Date:11/30/2016)... , Nov 30, 2016 Research and ... Intracranial Pressure Monitoring Devices 2017 - MedCore" report to their offering. ... , , ... brain and the skull. In healthy individuals, it is circulated though the ... are cases where the amount of CSF surrounding the brain changes significantly. ...
Breaking Medicine Technology: