Crystal Structure of the Bovine Mitochondrial Elongation Factor Tu·Ts Complex

• Published in: The Journal of biological chemistry 2005-02, Vol.280 (6), p.5071-5081
• Main Authors: Jeppesen, Mads Gravers, Navratil, Tomas, Spremulli, Linda Lucy, Nyborg, Jens
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M411782200

The three-dimensional structure of the bovine mitochondrial elongation factor (EF)-Tu·Ts complex (EF-Tumt·Tsmt) has been determined to 2.2-Å resolution using the multi-wavelength anomalous dispersion experimental method. This complex provides the first insight into the structure of EF-Tsmt. EF-Tsmt is similar to Escherichia coli and Thermus thermophilus EF-Ts in the amino-terminal domain. However, the structure of EF-Tsmt deviates considerably in the core domain with a five-stranded β-sheet forming a portion of subdomain N of the core. In E. coli EF-Ts, this region is composed of a three-stranded sheet. The coiled-coil domain of the E. coli EF-Ts is largely eroded in EF-Tsmt, in which it consists of a large loop packed against subdomain C of the core. The conformation of bovine EF-Tumt in complex with EF-Tsmt is distinct from its conformation in the EF-Tumt·GDP complex. When domain III of bovine EF-Tumt·GDP is superimposed on domain III of EF-Tumt in the EF-Tumt·Tsmt complex, helix B from domain I is also almost superimposed. However, the rest of domain I is rotated relative to this helix toward domain II, which itself is rotated toward domain I relative to domain III. Extensive contacts are observed between the amino-terminal domain of EF-Tsmt and domain I of EF-Tumt. Furthermore, the conserved TDFV sequence of EF-Tsmt also contacts domain I with the side chain of Asp139 contacting helix B of EF-Tumt and inserting the side chain of Phe140 between helices B and C. The structure of the EF-Tumt·Tsmt complex provides new insights into the nucleotide exchange mechanism and provides a framework for explaining much of the mutational data obtained for this complex.