2PMF

The crystal structure of a human glycyl-tRNA synthetase mutant

2PMF の概要

• エントリーDOI: 10.2210/pdb2pmf/pdb
• 分子名称: Glycyl-tRNA synthetase, CHLORIDE ION, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: classiia aminoacyl-trna synthetase, ligase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm : P41250
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 78932.52

構造登録者

Xie, W. (登録日: 2007-04-21, 公開日: 2007-05-22, 最終更新日: 2024-04-03)

主引用文献

Xie, W.,Nangle, L.A.,Zhang, W.,Schimmel, P.,Yang, X.L.
Long-range structural effects of a Charcot-Marie- Tooth disease-causing mutation in human glycyl-tRNA synthetase.
Proc.Natl.Acad.Sci.Usa, 104:9976-9981, 2007

PubMed Abstract: Functional expansion of specific tRNA synthetases in higher organisms is well documented. These additional functions may explain why dominant mutations in glycyl-tRNA synthetase (GlyRS) and tyrosyl-tRNA synthetase cause Charcot-Marie-Tooth (CMT) disease, the most common heritable disease of the peripheral nervous system. At least 10 disease-causing mutant alleles of GlyRS have been annotated. These mutations scatter broadly across the primary sequence and have no apparent unifying connection. Here we report the structure of wild type and a CMT-causing mutant (G526R) of homodimeric human GlyRS. The mutation is at the site for synthesis of glycyl-adenylate, but the rest of the two structures are closely similar. Significantly, the mutant form diffracts to a higher resolution and has a greater dimer interface. The extra dimer interactions are located approximately 30 A away from the G526R mutation. Direct experiments confirm the tighter dimer interaction of the G526R protein. The results suggest the possible importance of subtle, long-range structural effects of CMT-causing mutations at the dimer interface. From analysis of a third crystal, an appended motif, found in higher eukaryote GlyRSs, seems not to have a role in these long-range effects.

PubMed: 17545306
DOI: 10.1073/pnas.0703908104

実験手法

X-RAY DIFFRACTION (2.85 Å)