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

The researcher Manuel Palacn, head of the Heterogenic and Multigenic Diseases lab at the Institute for Research in Biomedicine (IRB), in Barcelona, is among the world's experts in HATs (heteromeric amino acid transporters).

In humans, there are eight HAT molecules. These are associated, for example, with the following: rare diseases called aminoacidurias, such as lysinuric protein intolerance and cystinuria; the development of infections caused by the Kaposi sarcoma virus; various types of cancer; and relapse in cocaine use. HATs are, as the name implies, amino acid transporters, and they exert their action in the cell membrane. Because of their nature, they are extremely difficult to crystallize and consequently no structural data are available for these molecules at the atomic level. However, for rational drug design this information is imperative.

A study published this week in the journal Proceedings of the National Academy of Sciences USA (PNAS) has revealed the first structure of one of the eight HATs. Achieved through collaboration between biochemists at IRB, experts in electronic microscopy at the University of Bern, and computational biologists in the Joint IRB-BSC Programme, this breakthrough paves the way for further research into the functions of the other seven HATs and the resolution of their structures. Moreover, this study provides the first sufficiently detailed structural data to tackle their inhibition through drugs.

HATs and human pathologies

HAT proteins are formed by two parts or subunits, a light one which serves to transport amino acids and a heavier one that allows movement of the complex to the cell membrane, conferring it stability. In humans, six transporters form a complex with 4F2hc, while two do so with rBAT, thus totalling eight HATs. "They are mini machines that are inserted into the membrane and are in constant movement, engulfing amino acids from the extracellular spac
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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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