Crystal structure of the EF-Tu.EF-Ts complex from Thermus thermophilus.
In order to study nucleotide exchange mechanisms in GTP-binding proteins, we have determined the crystal structure of the complex formed by the elongation factor Tu (EF-Tu) and its exchange factor Ts (EF-Ts) from Thermus thermophilus. The complex is a dyad symmetrical heterotetramer in which each EF-Tu, through a bipartite interface, interacts with two subunits of EF-Ts, explaining the need for a dimeric exchange factor. The architecture of the assembly is distinctly different from that of the corresponding heterodimeric E. coli complex, in which the monomeric E. coli EF-Ts remarkably forms essentially the same bipartite interface with EF-Tu through a sequence/structural repeat. GDP is released primarily by a Ts-induced peptide flip in the nucleotide binding pocket that disrupts hydrogen bonds to the phosphates and repositions the peptide carbonyl so as to sterically and electrostatically eject the GDP. The exchange mechanism may have useful implications for receptor-induced exchange in heterotrimeric G proteins.
Wang
Y
Y
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06511, USA.
Jiang
Y
Y
Meyering-Voss
M
M
Sprinzl
M
M
Sigler
P B
PB
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D019204:GTP-Binding Proteins / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010444:Peptide Elongation Factor Tu / Q000737:chemistry* / Q000378:metabolism; D010445:Peptide Elongation Factors / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D016963:Thermus thermophilus / Q000737:chemistry*
D001426:Bacterial Proteins; D010445:Peptide Elongation Factors; C023512:elongation factor Ts; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D010444:Peptide Elongation Factor Tu