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Albany 2001

category image Biomolecular
Stereodynamics
SUNY at Albany
June 19-23, 2001

Crystal Structure of Trbp111: a Structure-Specific tRNA Binding Protein

Trbp111 is a 111-amino acid structure-specific tRNA binding protein first identified in the extreme and ancient thermophile Aquifex aeolicus. Like elongation factor Tu, Trbp111 recognizes the intact L-shape of tRNA in a sequence non-specific manner. Throughout evolution, Trbp111 occurs as a highly conserved fusion module in proteins of diverse functions such as aminoacyl-tRNA synthetases, components of the eukaryotic multisynthetase complex involved in nuclear trafficking of tRNA, and two human cytokines (EMAP II and a tyrosyl-tRNA synthetase-derived human cytokine), linking protein synthesis with other cellular functions. We propose that Trbp111 is an ancient tRNA-binding element that might have played a role in the early evolution of the synthetase/tRNA recognition system.

The crystal structure of A. aeolicus Trbp111 and of its E. coli homolog have been determined at resolutions of 2.50 and 1.87 angstroms, respectively. The structure shows a symmetric dimer of two core domains, and a central dimerization domain where the N- and C-terminal regions of Trbp111 form an extensive dimer interface. The core of the monomer is a classical oligonucleotide/oligosaccharide-binding (OB) fold with a five-stranded b-barrel and a small capping helix. This structure is similar to that seen in the anticodon binding domain of three class II tRNA synthetases and several other proteins. Mutational analysis identified sites important for interactions with tRNA. These residues line the inner surfaces of two clefts formed between the b-barrel of each monomer and the dimer interface. Based on mutagenesis and tRNA footprint data, we propose a model for an asymmetric docking of the convex side of the tRNA molecule to the dimer.

The structure demonstrates that the widespread distribution of the Trbp111 domain comes from the remarkable versatility of the OB fold and its capacity to imbed into the framework of many different proteins, and thereby to carry out and connect together diverse cellular functions.

Manal A. Swairjo*(1), Arturo J. Morales (1, 2), Chien-Chia Wanh (1), Angel R. Ortiz (3, 4), and
Paul Schimmel(1)

Skaags Insti. for Chemical Biology (1), Depts of Mole. Biology and Chem. (1, 3), The Scripps,
La Jolla, CA 92037 USA.
Dept of Biology (2), MIT, Cambridge, MA 02139 USA.
*P: (858) 784-9486, Fax: (858) 784-8990, Email: swairjo@ scripps.edu