Functionally important sites in the elongation factor EF-Tu from Thermus aquaticus: analysis of fine structural changes upon binding of guanosine-3'-triphosphate and guanosine-3'-diphosphate
Brazhnikov, E.V.; Chirgadze, I.N.
Biofizika 46(6): 1027-1037
2001
ISSN/ISBN: 0006-3029 PMID: 11771276 Document Number: 536134
High-resolution data were used to analyze conformational changes of the main chain in two functional states of the ribosome elongation factor EF-Tu from Thermus aquaticus: the inactive state with guanosine-3'-diphosphate and the active state with guanosine-3'-triphosphate. Earlier only major changes in the effector loop of the domain I were determined. In this paper, all rearrangements in the main chain were observed upon shifting of C alpha-atoms from 1 to 8 A for each of the three protein domains. It was shown that these changes occur in numerous regions. New regions of changes were found, and they were located mostly in the loops of protein domains. Some of them are in the regions of interdomain interactions, others correlate with the known functionally important regions of EF-Tu binding with EF-Ts, aminoacyl-tRNA and the ribosome. Most changes induced by the conformational signal transfer from the guanosine-3'-triphosphate binding site occur just in the regions that are important for further stages of the factor functioning. The signal is transferred from domain I to domains II and III via interdomain contacts, predetermining fine fitting of functionally important regions to be involved in the following stages of the elongation cycle. The greatest part of the detected changes occurs in conservative residues of the whole family of bacterial factors, and only some of them are specific. This approach may prove useful for predetermining potential functionally important sites in other proteins.