Structure of the GDP Domain of EF-Tu and Location of the Amino Acids Homologous to ras Oncogene Proteins

• Published in: Science (American Association for the Advancement of Science) 1985-10, Vol.230 (4721), p.32-36
• Main Author: Jurnak, Frances
• Format: Article
• Language: English
• Subjects: Ambiguity; Amino Acid Sequence; Amino acids; Amino Acids - analysis; Astronomical maps; Atoms; Binding Sites; Biochemistry; Chemical Phenomena; Chemistry, Physical; Computers; Electron density; elongation factor Tu; Escherichia coli; Fourier Analysis; GDP; Guanine Nucleotides - analysis; Guanosine Diphosphate - analysis; Ligands; Magnesium - metabolism; Observations; Oncogenes; Peptide Elongation Factor Tu; Peptide Elongation Factors - analysis; Phosphates; Protein Conformation; Protein research; Solvents; Trypsin - metabolism; X-Ray Diffraction
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.3898365

A 2.7 angstrom resolution x-ray diffraction analysis of a trypsin-modified form of the Escherichia coli elongation factor Tu reveals that the GDP-binding domain has a structure similar to that of other nucleotide-binding proteins. The GDP ligand is located at the COOH-terminal end of the β sheet and is linked to the protein via a $Mg^{2+}$ ion salt bridge. The location of the guanine ring is unusual; the purine ring is located on the outer edge of the domain, not deep within a hydrophobic pocket. The amino acids from $Pro^{10}$to Arg$^{44}$ and from Gly $^{59}$ to Glu$^{190}$ have been assigned to the electron density with computer graphic techniques, and the resulting model is consistent with all known biochemical data. An analysis of the structure reveals that four regions of the amino acid sequence that are homologous with the family of ras oncogene proteins, termed p21, are located in the vicinity of the GDP-binding site, and most of the invariant amino acids shared by the proteins interact directly with the GDP ligand.