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Scientists discover structure of protein essential for quality control, nerve function
Date:1/14/2013

LA JOLLA, CA January 14, 2013 Using an innovative approach, scientists at The Scripps Research Institute (TSRI) have determined the structure of Ltn1, a recently discovered "quality-control" protein that is found in the cells of all plants, fungi and animals.

Ltn1 appears to be essential for keeping cells' protein-making machinery working smoothly. It may also be relevant to human neurodegenerative diseases, for an Ltn1 mutation in mice leads to a motor-neuron disease resembling amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease).

"To better understand Ltn1's mechanism of action, we needed to solve its structure, and that's what we've done here," said TSRI Associate Professor Claudio Joazeiro.

"In addition, this project has brought us a set of structural analysis techniques that we can apply to other exciting problems in biology," said TSRI Professor Bridget Carragher.

Joazeiro and Carragher, along with Clint Potter, also a TSRI professor, are senior authors of the new report, which appears in the online Early Edition of the Proceedings of the National Academy of Sciences the week of January 14, 2013.

Links to Neurodegenerative Disease

Ltn1 first turned up on biologists' radar screens several years ago when a joint Novartis-Phenomix research team noted that mice with an unknown gene mutation were born normal but suffered from progressive paralysis. The scientists dubbed the animals lister mice, because they listed to one side as they walked. Collaborating with Joazeiro, the Novartis team reported in a 2009 paper that the mutated gene normally codes for a type of enzyme known as an E3 ubiquitin ligase, and that the mouse phenotype was due to a neurodegenerative syndrome resembling ALS.

In a study published in the journal Nature the following year, Joazeiro and his postdoctoral research associate Mario H. Bengtson found that the enzyme serves as a crucial quality
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Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert  

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