Navigation Links
Rice lab finds molecular clues to Wilson disease
Date:8/19/2008

HOUSTON -- Aug. 19, 2008 -- Using a combination of computer simulations and cutting-edge lab experiments, physical biochemists at Rice University have discovered how a small genetic mutation -- which is known to cause Wilson disease -- subtly changes the structure of a large, complex protein that the body uses to keep copper from building up to toxic levels.

"The protein we study is like a big puzzle," said lead author Agustina Rodriguez-Granillo, the Rice doctoral student in biochemistry and cell biology who carried out the mathematical simulations and laboratory research. "The mutation that causes most cases of Wilson disease is well-known, but our study looks at the overall puzzle to see how such a small mutation can alter the shape and function of such a large and complex protein."

The protein in question is called ATP7B, which is a multidomain protein that sits in an internal membrane and regulates the movement of copper atoms inside human cells. Though large quantities of copper can be toxic, our bodies need a small amount for key enzymes involved in, for example, respiration and brain functions. ATP7B acts something like a warehouse manager, locking up bulk quantities of copper and handing it out for use in these proteins.

Wilson disease is a genetic disorder that alters the ATP7B protein's ability to work, causing copper to build up to toxic levels in the liver, brain, eyes and other organs. Over time the disease can cause life-threatening organ damage. Wilson disease affects as many as 150,000 people worldwide.

The new study is available online from the Journal of Molecular Biology. It focused on the genetic flaw that causes most cases of Wilson disease. That flaw, known as H1069Q, is caused when just one out of the more than 1,400 amino acids in ATP7B is changed. That amino acid is a histidine located at position 1069. In the disease-causing form of the protein, this histidine is replaced with a glutamic acid.

"This mutation occurs at a crucial location where the protein typically binds with a molecule called ATP that provides the energy the protein needs to move copper from place to place," said study co-author Pernilla Wittung-Stafshede, an adjunct professor of biochemistry and cell biology at Rice and Rodriguez-Granillo's adviser. Wittung-Stafshede, professor in chemistry at Umea University in Sweden, said, "Past studies have compared the behavior of the mutant protein with that of the nonmutant and found very little difference, so it was unclear how this small change led to the devastating effects that are seen in Wilson disease."

Using a combination of experimental data and computer simulations that looked specifically at a portion of the protein called the N-domain, where the H1069Q mutation occurs, Wittung-Stafshede, Rodriguez-Granillo and postdoctoral researcher Erik Sedlak (now at the University of Texas at San Antonio) confirmed that ATP's function was significantly reduced in the mutant form of the protein. They also found that the mutation caused structural changes in other sections of the protein that were far away from the mutation site. For example, the healthy form of the protein is capped with a large, flexible loop. The purpose of the loop is unknown, but its shape is altered and more compact in the diseased form of the protein.

"This implies that the loop has some importance, perhaps in regulation of ATP7B's activities, and we intend to follow up on this in our future studies," Rodriguez-Granillo said.


'/>"/>

Contact: Jade Boyd
jadeboyd@rice.edu
713-348-6778
Rice University
Source:Eurekalert  

Related biology news :

1. University of Oregon researcher finds that on waters surface, nitric acid is not so tough
2. Study finds environmental tests help predict hospital-acquired Legionnaires disease risk
3. Study finds blocking angiogenesis signaling from inside cell may lead to serious health problems
4. Study finds Viagra increases release of key reproductive hormone
5. Survey finds elevated rates of new asthma among WTC rescue and recovery workers
6. St. Jude finds factors that accelerate resistance to targeted therapy in lymphoblastic leukemia
7. Study finds a high rate of asthma in college athletes
8. Ecologist finds dire devastation of snake species following floods of 93, 95
9. Men shed light on the mystery of human longevity, study finds
10. JILA finds flaw in model describing DNA elasticity
11. Americans remain pessimistic about the environment, Stanford-AP survey finds
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Rice lab finds molecular clues to Wilson disease
(Date:3/11/2016)... , March 11, 2016 ... new market research report "Image Recognition Market by Technology ... (Marketing and Advertising), by Deployment Type (On-Premises and Cloud), ... To 2022", published by MarketsandMarkets, the global market is ... to USD 29.98 Billion by 2020, at a CAGR ...
(Date:3/9/2016)... March 9, 2016 This BCC Research report ... of the RNA Sequencing (RNA Seq) market for the ... instruments, tools and reagents, data analysis, and services. ... of the RNA-Sequencing market such as RNA-Sequencing tools and ... main factors affecting each segment and forecast their market ...
(Date:3/8/2016)... 8, 2016   Valencell , the leading ... it has secured $11M in Series D financing. ... new venture fund being launched by UAE-based financial ... existing investors TDF Ventures and WSJ Joshua Fund. ... its triple-digit growth and accelerate its pioneering innovation ...
Breaking Biology News(10 mins):
(Date:4/29/2016)... ... April 29, 2016 , ... Summit for Stem Cell has received a $250,000 ... patient-specific stem cell therapy for the treatment of Parkinson’s disease. The Summit research project ... The Scripps Research Institute in San Diego, CA. , The aim of ...
(Date:4/28/2016)... , ... April 28, 2016 , ... ... ongoing support for Connecticut's innovative, growing companies, today announced the launch of ... financial technology (fintech) companies. , “VentureClash looks to attract the best ...
(Date:4/27/2016)... ... 27, 2016 , ... Shimadzu Scientific Instruments (SSI) will be ... Business Conference and Expo. Shimadzu’s high-performance instruments enable laboratories to test cannabis products ... can stop by booth 1021 to learn how Shimadzu’s instruments can help improve ...
(Date:4/27/2016)... ... 27, 2016 , ... The Board of Directors of Biohaven ... Tilton as Chief Commercial Officer.  Mr. Tilton joined Biohaven from Alexion Pharmaceuticals, Inc. ... responsible for the commercialization of multiple orphan drug indications. Mr. Tilton has ...
Breaking Biology Technology: