AN ALPHA TO BETA CONFORMATIONAL SWITCH IN EF-TU

Background: The bacterial elongation factor EF-Tu recognizes and trans ports aminoacyl-tRNAs to mRNA-programmed ribosomes. EF-Tu shares many structural and functional properties with other GTPases whose conforma tions are regulated by guanine nucleotides. Results: An intact form of Escherichia coli EF-Tu complexed with GDP has been crystallized in th e presence of the EF-Tu-specific antibiotic GE2270 A, The three-dimens ional structure has been solved by X-ray diffraction analysis and refi ned to a final crystallographic R factor of 17.2% at a resolution of 2 .5 Angstrom. The location of the GE2270 A antibiotic-binding site coul d not be identified. Conclusions: The structure of EF-Tu-GDP is nearly identical to that of a trypsin-modified form of EF-Tu-GDP, demonstrat ing conclusively that the protease treatment had not altered any essen tial structural features. The present structure represents the first v iew of an ordered Switch I region in EF-Tu-GDP and reveals similaritie s 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 form s of EF-Tu also reveals that a segment, six amino acids in length, com pletely converts from an a helix in the GTP complex to beta secondary structure in the GDP form. The alpha to beta switch in EF-Tu may repre sent a prototypical activation mechanism for other protein families.