Crystal structure of the bovine mitochondrial elongation factor Tu.Ts complex

The three-dimensional structure of the bovine mitochondrial elongation factor (EF)-Tu-Ts complex (EF-Tu(mt).Ts-mt) has been determined to 2.2-Angstrom resolution using the multi-wavelength anomalous dispersion experimental method. This complex provides the first insight into the structure of EF-Ts-mt.. EF-Ts-mt is similar to Escherichia coli and Thermus thermophilus EF-Ts in the amino-terminal domain. However, the structure of EF-Ts-mt deviates considerably in the core domain with a five-stranded beta-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-Ts-mt, in which it consists of a large loop packed against subdomain C of the core. The conformation of bovine EF-Tu(mt) in complex with EF-Ts-mt is distinct from its conformation in the EF-Tu(mt)-GDP complex. When domain III of bovine EF-Tu(mt).GDP is superimposed on domain III of EF-Tu(mt) in the EF-Tu(mt).Ts-mt complex, helix B from domain I is also almost superimposed. However, the rest of domain I is rotated relative to this helix toward domain 11, 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-Tu(mt). Furthermore, the conserved TDFV sequence of EF-Tsmt also contacts domain I with the side chain of Asp (139) contacting helix B of EF-Tu(mt) and inserting the side chain of Phe(140) between helices B and C. The structure of the EF-Tu(mt).Ts-mt complex provides new insights into the nucleotide exchange mechanism and provides a framework for explaining much of the mutational data obtained for this complex.