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First observation of a human HAT, key proteins in numerous pathologies
Date:2/11/2014

e and releasing them in the cytoplasm or vice-versa," explains Palacn. "We knew the structure of one of the parts. Now, for the first time, we have the low resolution of the entire complex," he says.

The study, whose first four authors include the post-doctoral researcher Albert Rosell and the PhD student Elena lvarez-Marimon at IRB Barcelona, describes the structure of the 4F2hc/LAT2 complex. "We chose this complex because it shows the highest stability among human HATs and would allow a greater chance of tackling its structure. The next step is to move onto its atomic resolution," explains Rosell. "Resolution at this level, at the highest definition, will help us to study the details of how "the machine" works and to gain a greater knowledge regarding the precise drug targets," add the scientists.

Only some HATs are associated with diseases. The 4F2hc/LAT1 and 4F2hc/xCT complexes are overexpressed in many kinds of cancer. "We have better and more detailed knowledge about the complexes and so we are providing new options by which to deal with cancer," says Manuel Palacn. The lab also focuses on aminoacidurias. Mutation in the 4F2hc/y+LAT1 complex causes lysinuric protein intolerance, a rare disease with 200 known cases. Finally, mutations in the rBAT/b(0,+)AT complex lead to cystinuria, a condition with an estimated incidence of one case per 7,000 births.

Manuel Palacn's basic research into HATs seeks to identify new therapeutic targets and to improve diagnostic tools for all conditions that involve HATs, with a special focus on aminoacidurias.

The study started as part of the European project EDICT (European Drug Initiative on Channels and Transporters), a consortium comprising 21 groups and funded by 11 million euros, which aims to increase the database of membrane protein structures. In 2008, at the beginning of the project, about 100 membrane protein structures were known. Today, this number has tripled, Palacn's group having
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Contact: Sònia Armengou
armengou@irbbarcelona.org
34-934-037-255
Institute for Research in Biomedicine (IRB Barcelona)
Source:Eurekalert  

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