An α to β conformational switch in EF-Tu

• Published in: Structure (London) Vol. 4; no. 10; pp. 1153 - 1159
• Main Authors: Abel, Kenton, Yoder, Marilyn D, Hilgenfeld, Rolf, Jurnak, Frances
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.10.1996
• Subjects: Anti-Bacterial Agents - chemistry; Bacterial Proteins - chemistry; Crystallography, X-Ray; EF-Tu–GDP; EF-Tu–GTP; elongation factor structure; Escherichia coli; GTP Phosphohydrolase-Linked Elongation Factors - chemistry; Guanosine Diphosphate - chemistry; Guanosine Triphosphate - chemistry; Peptide Elongation Factor Tu - chemistry; Peptides, Cyclic - chemistry; Protein Conformation; Species Specificity; Thiazoles - chemistry; α to β conformational switch; elongation factor structure; EF-Tu–GDP; EF-Tu–GTP; α to β conformational switch
• ISSN: 0969-2126; 1878-4186
• DOI: 10.1016/S0969-2126(96)00123-2

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 å. 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.