An α to β conformational switch in EF-Tu

Abstract Background The bacterial elongation factor EF-Tu recognizes and transports aminoacyl-tRNAs to mRNA-programmed ribosomes. EF-Tu shares many structural and functional properties with other GTPases whose conformations are regulated by guanine nucleotides. Results An intact form of Escherichia coli EF-Tu complexed with GDP has been crystallized in the presence of the EF-Tu-specific antibiotic GE2270 A. The three-dimensional structure has been solved by X-ray diffraction analysis and refined to a final crystallographic R factor of 17.2% at a resolution of 2.5 a. The location of the GE2270 A antibiotic-binding site could not be identified. Conclusions The structure of EF-Tu–GDP is nearly identical to that of a trypsin-modified form of EF-Tu–GDP, demonstrating conclusively that the protease treatment had not altered any essential structural features. The present structure represents the first view of an ordered Switch I region in EF-Tu–GDP and reveals similarities with two other GTPases complexed with GDP: Ran and ADP-ribosylation factor-1. A comparison of the Switch I regions of the GTP and GDP forms of EF-Tu also reveals that a segment, six amino acids in length, completely converts from an α helix in the GTP complex to β secondary structure in the GDP form. The α to β switch in EF-Tu may represent a prototypical activation mechanism for other protein families.

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