Featured Research

from universities, journals, and other organizations

First observation of a human HAT, key proteins in numerous pathologies

Date:
February 11, 2014
Source:
Institute for Research in Biomedicine (IRB Barcelona)
Summary:
A study published this week has revealed the first structure of one of the eight human HATs. HAT amino acid transporters are involved in pathologies such as aminoacidurias, cancer, viral infections and cocaine addiction. This breakthrough paves the way for further research into the functions of the other seven HATs and the resolution of their structures. Moreover, it provides the first sufficiently detailed structural data to tackle their inhibition through drugs.

The researcher Manuel Palacín, 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).

Related Articles


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 space and releasing them in the cytoplasm or vice-versa," explains Palacín. "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 Álvarez-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 Palacín. 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 Palacín'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.


Story Source:

The above story is based on materials provided by Institute for Research in Biomedicine (IRB Barcelona). Note: Materials may be edited for content and length.


Journal Reference:

  1. Albert Rosell, Marcel Meury, Elena Álvarez-Marimon, Meritxell Costa, Laura Pérez-Cano, Antonio Zorzano, Juan Fernández-Recio, Manuel Palacín and Dimitrios Fotiadis. Structural bases for the interaction and stabilization of the human amino acid transporter LAT2 with its ancillary protein 4F2hc. Proceedings of the National Academy of Sciences, February 2014 DOI: 10.1038/nbt.2831

Cite This Page:

Institute for Research in Biomedicine (IRB Barcelona). "First observation of a human HAT, key proteins in numerous pathologies." ScienceDaily. ScienceDaily, 11 February 2014. <www.sciencedaily.com/releases/2014/02/140211113835.htm>.
Institute for Research in Biomedicine (IRB Barcelona). (2014, February 11). First observation of a human HAT, key proteins in numerous pathologies. ScienceDaily. Retrieved January 29, 2015 from www.sciencedaily.com/releases/2014/02/140211113835.htm
Institute for Research in Biomedicine (IRB Barcelona). "First observation of a human HAT, key proteins in numerous pathologies." ScienceDaily. www.sciencedaily.com/releases/2014/02/140211113835.htm (accessed January 29, 2015).

Share This


More From ScienceDaily



More Plants & Animals News

Thursday, January 29, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Brawling Pandas Are Violently Adorable

Brawling Pandas Are Violently Adorable

Buzz60 (Jan. 29, 2015) — Video of pandas play fighting at the Chengdu Research Base in China will make your day. Mara Montalbano (@maramontalbano) shows us. Video provided by Buzz60
Powered by NewsLook.com
Why Researchers Say We Should Cut Back On Biofuels

Why Researchers Say We Should Cut Back On Biofuels

Newsy (Jan. 29, 2015) — Biofuels aren&apos;t the best alternative to fossil fuels, according to a new report. In fact, they&apos;re quite a bad one. Video provided by Newsy
Powered by NewsLook.com
3-D Printed Wheelchair Helps Two-Legged Dog Learn to Run

3-D Printed Wheelchair Helps Two-Legged Dog Learn to Run

Buzz60 (Jan. 29, 2015) — 3-D printing helps another two-legged dog run around with his four-legged friends. Jen Markham (@jenmarkham) has the adorable video. Video provided by Buzz60
Powered by NewsLook.com
Dogs Bring on So Many Different Emotions in Their Human Best Friends

Dogs Bring on So Many Different Emotions in Their Human Best Friends

RightThisMinute (Jan. 28, 2015) — From new-puppy happy tears to helpful-grocery-carrying-dog laughter, our four-legged best friends can make us feel the entire spectrum of emotions. Video provided by RightThisMinute
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Plants & Animals

Earth & Climate

Fossils & Ruins

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins