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The crystal structure of human GlnRS provides basis for the development of neurological disorders [electronic resource].

Published
Washington, D.C. : United States. Dept. of Energy. Office of Basic Energy Sciences, 2016.
Oak Ridge, Tenn. : Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy
Physical Description
pages 3,420-3,431 : digital, PDF file
Additional Creators
United States. Department of Energy. Office of Basic Energy Sciences, National Cancer Institute (U.S.), National Institutes of Health (U.S.), University of Texas at Austin, and United States. Department of Energy. Office of Scientific and Technical Information
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Summary
Cytosolic glutaminyl-tRNA synthetase (GlnRS) is the singular enzyme responsible for translation of glutamine codons. Compound heterozygous mutations in GlnRS cause severe brain disorders by a poorly understood mechanism. Herein, we present crystal structures of the wild type and two pathological mutants of human GlnRS, which reveal, for the first time, the domain organization of the intact enzyme and the structure of the functionally important N-terminal domain (NTD). Pathological mutations mapping in the NTD alter the domain structure, and decrease catalytic activity and stability of GlnRS, whereas missense mutations in the catalytic domain induce misfolding of the enzyme. Our results suggest that the reduced catalytic efficiency and a propensity of GlnRS mutants to misfold trigger the disease development. As a result, this report broadens the spectrum of brain pathologies elicited by protein misfolding and provides a paradigm for understanding the role of mutations in aminoacyl-tRNA synthetases in neurological diseases. Keywords
Report Numbers
E 1.99:1262023
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Note
Published through SciTech Connect.
02/10/2016.
Nucleic Acids Research 44 7 ISSN 0305-1048 AM
Jana Ognjenovic; Jiang Wu; Doreen Matthies; Ulrich Baxa; Sriram Subramaniam; Jiqiang Ling; Miljan Simonovic.
Univ. of Texas, Houston, TX (United States)
Michigan Economic Development Corporation
Michigan Technology Tri-Corridor
Funding Information
AC02-06CH11357
View MARC record | catkey: 23500584