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.
"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!
Hopkins researchers ID neurotransmitter that helps cancers progress
26.04.2019 | Johns Hopkins Medicine
Trigger region found for absence epileptic seizures
25.04.2019 | RIKEN
For the first time, physicists at the University of Basel have succeeded in measuring the magnetic properties of atomically thin van der Waals materials on the nanoscale. They used diamond quantum sensors to determine the strength of the magnetization of individual atomic layers of the material chromium triiodide. In addition, they found a long-sought explanation for the unusual magnetic properties of the material. The journal Science has published the findings.
The use of atomically thin, two-dimensional van der Waals materials promises innovations in numerous fields in science and technology. Scientists around the...
Flexible, organic and printed electronics conquer everyday life. The forecasts for growth promise increasing markets and opportunities for the industry. In Europe, top institutions and companies are engaged in research and further development of these technologies for tomorrow's markets and applications. However, access by SMEs is difficult. The European project SmartEEs - Smart Emerging Electronics Servicing works on the establishment of a European innovation network, which supports both the access to competences as well as the support of the enterprises with the assumption of innovations and the progress up to the commercialization.
It surrounds us and almost unconsciously accompanies us through everyday life - printed electronics. It starts with smart labels or RFID tags in clothing, we...
The human eye is particularly sensitive to green, but less sensitive to blue and red. Chemists led by Hubert Huppertz at the University of Innsbruck have now developed a new red phosphor whose light is well perceived by the eye. This increases the light yield of white LEDs by around one sixth, which can significantly improve the energy efficiency of lighting systems.
Light emitting diodes or LEDs are only able to produce light of a certain colour. However, white light can be created using different colour mixing processes.
Researchers led by Francesca Ferlaino from the University of Innsbruck and the Austrian Academy of Sciences report in Physical Review X on the observation of supersolid behavior in dipolar quantum gases of erbium and dysprosium. In the dysprosium gas these properties are unprecedentedly long-lived. This sets the stage for future investigations into the nature of this exotic phase of matter.
Supersolidity is a paradoxical state where the matter is both crystallized and superfluid. Predicted 50 years ago, such a counter-intuitive phase, featuring...
A stellar flare 10 times more powerful than anything seen on our sun has burst from an ultracool star almost the same size as Jupiter
17.04.2019 | Event News
15.04.2019 | Event News
09.04.2019 | Event News
26.04.2019 | Life Sciences
26.04.2019 | Physics and Astronomy
26.04.2019 | Physics and Astronomy