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Breaking down Huntington's disease one protein at a time
Date:2/4/2008

BLOOMINGTON, Ind. -- 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.

"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
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Contact: Joel Ybe
jybe@bio.indiana.edu
812-856-4882
Indiana University
Source:Eurekalert  

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