Wen Li, Leonardo G. Trabuco, Klaus Schulten, and Joachim Frank.
Molecular dynamics of EF-G during translocation.
PROTEINS: Structure, Function, and Bioinformatics,
79:1478-1486, 2011.
LI2011
Elongation factor G (EF-G) plays a crucial role in two stages of mRNA-(tRNA)2
translocation. First, EF-G•GTP enters the pretranslocational ribosome in its intersubunit-
rotated state, with tRNAs in their hybrid (P/E, A/P) positions. Second, a conformational
change in EF-G’s domain IV induced by GTP hydrolysis disengages the mRNA-anticodon
stem-loops of the tRNAs from the decoding center to advance relative to the small subunit
when the ribosome undergoes a backward inter-subunit rotation. These events take place
as EF-G undergoes a series of large conformational changes as visualized by cryo-EM and
X-ray studies. The number and variety of these structures leave open many questions on
how these different configurations form during the dynamic translocation process. To
understand the molecular mechanism of translocation, we examined the molecular
motions of EF-G in solution by means of molecular dynamics simulations. Our results
show: (1) rotations of the super-domain formed by domains III-V with respect to the
super-domain formed by I-II, and rotations of domain IV with respect to domain
III; (2) flexible conformations of both 503- and 575-loops; (3) large conformational
variability in the bound form provided by the interaction between domain V and the
GTPase-associated center; (4) after GTP hydrolysis, the switch I region seems to be
instrumental for effecting the conformational change at the end of domain IV implicated in
the disengagement of the codonanticodon helix from the decoding center.
