4YE6: The Crystal Structure Of The Intact Human Glnrs

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. 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.
PDB ID: 4YE6Download
MMDB ID: 136549
PDB Deposition Date: 2015/2/23
Updated in MMDB: 2017/10
Experimental Method:
x-ray diffraction
Resolution: 2.4  Å
Source Organism:
Similar Structures:
Biological Unit for 4YE6: monomeric; determined by author and by software (PISA)
Molecular Components in 4YE6
Label Count Molecule
Protein (1 molecule)
Glutamine--trna Ligase(Gene symbol: QARS)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB