2PMF

The crystal structure of a human glycyl-tRNA synthetase mutant

Summary for 2PMF

• Entry DOI: 10.2210/pdb2pmf/pdb
• Descriptor: Glycyl-tRNA synthetase, CHLORIDE ION, GLYCEROL, ... (4 entities in total)
• Functional Keywords: classiia aminoacyl-trna synthetase, ligase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : P41250
• Total number of polymer chains: 1
• Total formula weight: 78932.52

Authors

Xie, W. (deposition date: 2007-04-21, release date: 2007-05-22, Last modification date: 2024-04-03)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.85 Å)