3VBB

Crystal Structure of Seryl-tRNA Synthetase from Human at 2.9 angstroms

Summary for 3VBB

• Entry DOI: 10.2210/pdb3vbb/pdb
• Descriptor: Seryl-tRNA synthetase, cytoplasmic, MAGNESIUM ION, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: coiled-coil, ligase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P49591
• Total number of polymer chains: 6
• Total formula weight: 360224.71

Authors

Xu, X.L.,Yang, X.-L. (deposition date: 2012-01-02, release date: 2012-02-29, Last modification date: 2023-09-13)

Primary citation

Xu, X.,Shi, Y.,Zhang, H.M.,Swindell, E.C.,Marshall, A.G.,Guo, M.,Kishi, S.,Yang, X.L.
Unique domain appended to vertebrate tRNA synthetase is essential for vascular development.
Nat Commun, 3:681-681, 2012

PubMed Abstract: New domains were progressively added to cytoplasmic aminoacyl transfer RNA (tRNA) synthetases during evolution. One example is the UNE-S domain, appended to seryl-tRNA synthetase (SerRS) in species that developed closed circulatory systems. Here we show using solution and crystal structure analyses and in vitro and in vivo functional studies that UNE-S harbours a robust nuclear localization signal (NLS) directing SerRS to the nucleus where it attenuates vascular endothelial growth factor A expression. We also show that SerRS mutants previously linked to vasculature abnormalities either deleted the NLS or have the NLS sequestered in an alternative conformation. A structure-based second-site mutation, designed to release the sequestered NLS, restored normal vasculature. Thus, the essential function of SerRS in vascular development depends on UNE-S. These results are the first to show an essential role for a tRNA synthetase-associated appended domain at the organism level, and suggest that acquisition of UNE-S has a role in the establishment of the closed circulatory systems of vertebrates.

PubMed: 22353712
DOI: 10.1038/ncomms1686

Experimental method

X-RAY DIFFRACTION (2.891 Å)