By comparing the three-dimensional structure of EF-Tu in its GTP-bound and GDP-bound forms, we can see how the repositioning of the tRNA occurs. The dissociation of the inorganic phosphate group (Pi), which follows the reaction GTP →GDP + Pi, causes a shift of a few tenths of a nanometer at the GTP-binding site, just as it does in the Ras protein. This tiny movement, equivalent to a few times the diameter of a hydrogen atom, causes a conformational change to propagate along a crucial piece of αhelix, called the switch helix, in the Ras-like domain of the protein. The switch helix seems to serve as a latch that adheres to a specific site in another domain of the molecule, holding the protein in a “shut” conformation. The conformational change triggered by GTP hydrolysis causes the switch helix to detach, allowing separate domains of the protein to swing apart, through a distance of about 4 nm (Figure 3–72). This releases the bound tRNA molecule, allowing its attached amino acid to be used (Figure 3–73).
Notice in this example how cells have exploited a simple chemical change that occurs on the surface of a small protein domain to create a movement 50 times larger. Dramatic shape changes of this type also cause the very large movements that occur in motor proteins, as we discuss next.
We have seen that conformational changes in proteins have a central role in enzyme regulation and cell signaling. We now discuss proteins whose major function is to move other molecules. These motor proteins generate the forces responsible for muscle contraction and the crawling and swimming of cells. Motor proteins also power smaller-scale intracellular movements: they help to move chromosomes to opposite ends of the cell during mitosis (discussed in Chapter 17), to move organelles along molecular tracks within the cell (discussed in Chapter 16), and to move enzymes along a DNA strand during the synthesis of a new DNA molecule (discussed in Chapter 5). All these fundamental processes depend on proteins with moving parts that operate as force-generating machines.
How do these machines work? In other words, how do cells use shape changes in proteins to generate directed movements? If, for example, a protein is required to walk along a narrow thread such as a DNA molecule, it can do this by undergoing a series of conformational changes, such as those shown in Figure 3–74. But with nothing to drive these changes in an orderly sequence, they are perfectly
Figure 3–73 an aminoacyl tRna molecule bound to eF-Tu. Note how the bound protein blocks the use of the tRNA-linked amino acid (green) for protein synthesis until GTP hydrolysis triggers the conformational changes shown in Figure 3–72C, dissociating the protein-tRNA complex. EF-Tu is a bacterial protein; however, a very similar protein exists in eukaryotes, where it is called EF-1 (Movie 3.12). (Coordinates determined by P. Nissen et al., Science 270:1464–1472, 1995. PDB code: 1B23.) 162 Chapter 3:  Proteins reversible, and the protein can only wander randomly back and forth along the thread. We can look at this situation in another way. Since the directional movement of a protein does work, the laws of thermodynamics (discussed in Chapter 2) demand that such movement use free energy from some other source (otherwise the protein could be used to make a perpetual motion machine). Therefore, without an input of energy, the protein molecule can only wander aimlessly.