Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Breaking down Huntington's disease one protein at a time

06.02.2008
Hoping to piece together the intricate series of interactions that lead to Huntington's disease, Indiana University Bloomington scientists have determined the shape and structure of a binding site that may prove useful in combating the neurodegenerative disease.

In the Feb. 1 issue of Journal of Molecular Biology, IU Bloomington biologists Joel Ybe and Qian Niu describe a region on the surface of HIP1 (Huntingtin-interacting protein 1) that could bind HIPPI (HIP1-protein interactor). The association of HIP1 and HIPPI is believed to lead to the degeneration of nerve cells.

"If we now think that this is the region where HIPPI binds, we could eventually design a drug that can come in and sit down between these two proteins, which would prevent the binding of HIPPI," said Ybe, who led the research.

Ybe and Niu's paper is the first to scrutinize a Huntington's disease-related protein's structure and function at the molecular level. Ybe and colleagues hope meticulous study of each Huntington's disease protein will suggest new avenues for wholesale prevention.

... more about:
»HIP1 »HIPPI »Huntington' »Ybe »bind »binding »clathrin »nutrients »structure

"The important thing for us is to come up with something that will potentially help people," said Ybe. "What is happening before the manifestation of the disease? Can we use this information to come up with drugs to diffuse that process?"

Huntington's disease is a hereditary disorder that causes large numbers of nerve cells to die. About 30,000 people in the U.S. are estimated to have the disease -- approximately one person in ten thousand. Symptoms include uncontrolled movements, dementia and depression, but these symptoms do not usually appear until the afflicted reach their 30s or 40s. Despite major strides forward in understanding the disease in recent years, there is currently no cure.

The disease begins when the huntingtin protein falls off HIP1. The vacancy allows another protein, HIPPI, to then bind to HIP1. The complex of HIP1 and HIPPI is responsible for activating other proteins that cause the death of cells. The loss of large amounts of nerve cells leads to a loss of motor function, and eventually brain function, too.

Ybe and Niu used X-ray crystallography to look at an area of interest on the surface of HIP1, which works in concert with clathrin to traffic nutrients into a cell, and has long been implicated as playing an important role in the development of Huntington's disease. They learned that the potential binding surface of HIPPI in HIP1 has an unexpected shape for a binding site, a spiraling spiral called a "coiled coil." This finding was contrary to predicted results that the binding surface that receives HIPPI is folded into a so-called death effector domain.

Using the information from the published molecular structure of HIP1, IU biologists hope to be able to test which protein connections are ultimately responsible for triggering the chain of interactions leading to Huntington's disease and how to block them. For example, they observed that clathrin, protein involved in bringing nutrients to the cell, binds with HIP1 right next door to where HIPPI binds. While clathrin "packages" nutrients for a cell, HIP1 connects these "baskets" to the structure of the cell. If HIPPI binding with HIP1 prevents clathrin connection with HIP1, then the normal pathway of nutrients into a cell is interrupted, causing changes in the cells ability to function normally.

"Until we understand the relationship between huntingtin protein, HIP1, clathrin and HIPPI -- we are not going to understand what is happening in the person who has the disease," says Ybe. "You understand what's going on in healthy cells, before you understand what's going on in diseased cells."

Joel Ybe | EurekAlert!
Further information:
http://www.indiana.edu

Further reports about: HIP1 HIPPI Huntington' Ybe bind binding clathrin nutrients structure

More articles from Life Sciences:

nachricht Hunting pathogens at full force
22.03.2017 | Helmholtz-Zentrum für Infektionsforschung

nachricht A 155 carat diamond with 92 mm diameter
22.03.2017 | Universität Augsburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

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...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

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

Pulverizing electronic waste is green, clean -- and cold

22.03.2017 | Materials Sciences

Astronomers hazard a ride in a 'drifting carousel' to understand pulsating stars

22.03.2017 | Physics and Astronomy

New gel-like coating beefs up the performance of lithium-sulfur batteries

22.03.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>