CRYSTALLOGRAPHIC STUDIES OF ELONGATION-FACTOR-G

The elongation factors G (EF-G) and Tu (EF-Tu) go through a number of conformation states in their functional cycles. Since they both are GT Pases, have similar G domains and domains II, and have similar interac tions with the nucleotides, then GTP hydrolysis must occur in similar ways. The crystal structures of two conformational states are known fo r EF-G and three are known for EF-Tu. The conformations of EF-G . GDP and EF-Tu . GTP are closely related. EF-Tu goes through a large confor mational change upon GTP cleavage. This conformational change is to la rge extent due to an altered interaction between the G domain and doma ins II and III. II and III. A number of kirromycin-resistant mutations are situated at the interface between domains I and m. The interface between the G domain and domain V in EF-G corresponds with this dynami c interface in EF-Tu. The contact area in EF-G is small and dominated by interactions between charged amino acids, which are parr of a syste m that is observed to undergo conformational changes. Furthermore, a n umber of fusidic acid resistant mutants have been identified in this a rea. All of this evidence makes it likely that EF-G undergoes a large conformational change in its functional cycle. If the structures and c onformational states of the elongation factors are related to a scheme in which the ribosome oscillates between two conformations, the pretr anslocational and posttranslocational states, a model is arrived at in which EF-Tu drives the reaction in one direction and EF-G in the oppo site. This may lead to the consequence that the GTP state of one facto r is similar to the GDP state of the other. At the GTP hydrolysis stat e, the structures of the factors will be close to superimposable.