What Berger and Thomsen found from their structural studies was that nucleic-acid binding elements in the interior of the Rho ring spiral around six bases of RNA. When the ATP binding sites that are coupled to this RNA segment release their chemical energy through hydrolysis of the nucleotide, they do so in a sequential manner that propagates around the hexameric ring. This chemical energy is converted into mechanical motion that dictates the rotational direction of the Rho motor based on the firing order of the ATP sites.
"Think of it like the cylinders in a radial engine," Berger says. "The fuel and intake come in from one side, leading to motions that cause the cylinders to spin around a central RNA camshaft. However, because the cylinders actually lie out of plane, they walk along the camshaft as they move."
In their study, Berger and Thomsen found that nature has evolved a similar rotary mechanism for the papillomavirus E1 protein, an AAA+ family hexameric helicase. Their analysis showed that E1 motor moves in the opposite direction along a nucleic chain because the rotational firing order of ATP sites is actually reversed. Determining the molecular structure of protein motors and learning how they operate is critical not only to basic understanding of the molecular principles that control the cell, but also to aiding pharmaceutical drug discovery efforts.
"DNA and RNA are large and cumbersome macromolecular polymers which present a challenge to the molecular machines that need to access their genetic information," says Berger. "There have been two other proposed models for these protein motors in addition to the rotary, one a type of putt-putt motor, in which all the active binding elements hydrolyze ATP simultaneously, and the other a stochastic model, whereby A
|Contact: Lynn Yarris|
DOE/Lawrence Berkeley National Laboratory