3TUP

Crystal structure of human mitochondrial PheRS complexed with tRNAPhe in the active open state

Summary for 3TUP

• Entry DOI: 10.2210/pdb3tup/pdb
• Related: 1PYS 3CMQ
• Descriptor: Phenylalanyl-tRNA synthetase, mitochondrial, Thermus thermophilus tRNAPhe (2 entities in total)
• Functional Keywords: class ii aars, rrm fold, aminoacylation, mitochondria, ligase-rna complex, ligase/rna
• Biological source: Homo sapiens (human); More
• Cellular location: Mitochondrion matrix (Potential): O95363
• Total number of polymer chains: 2
• Total formula weight: 72992.57

Authors

Safro, M.,Klipcan, L.,Moor, N.,Finarov, I.,Kessler, N.,Sukhanova, M. (deposition date: 2011-09-17, release date: 2011-11-23, Last modification date: 2024-02-28)

Primary citation

Klipcan, L.,Moor, N.,Finarov, I.,Kessler, N.,Sukhanova, M.,Safro, M.G.
Crystal Structure of Human Mitochondrial PheRS Complexed with tRNA(Phe) in the Active "Open" State.
J.Mol.Biol., 415:527-537, 2012

PubMed Abstract: Monomeric human mitochondrial phenylalanyl-tRNA synthetase (PheRS), or hmPheRS, is the smallest known enzyme exhibiting aminoacylation activity. HmPheRS consists of only two structural domains and differs markedly from heterodimeric eukaryotic cytosolic and bacterial analogs both in the domain organization and in the mode of tRNA binding. Here, we describe the first crystal structure of mitochondrial aminoacyl-tRNA synthetase (aaRS) complexed with tRNA at a resolution of 3.0 Å. Unlike bacterial PheRSs, the hmPheRS recognizes C74, the G1-C72 base pair, and the "discriminator" base A73, proposed to contribute to tRNA(Phe) identity in the yeast mitochondrial enzyme. An interaction of the tRNA acceptor stem with the signature motif 2 residues of hmPheRS is of critical importance for the stabilization of the CCA-extended conformation and its correct placement in the synthetic site of the enzyme. The crystal structure of hmPheRS-tRNA(Phe) provides direct evidence that the formation of the complex with tRNA requires a significant rearrangement of the anticodon-binding domain from the "closed" to the productive "open" state. Global repositioning of the domain is tRNA modulated and governed by long-range electrostatic interactions.

PubMed: 22137894
DOI: 10.1016/j.jmb.2011.11.029

Experimental method

X-RAY DIFFRACTION (3.05 Å)