Another Rotary Machine Found in Bacteria

first_imgA molecular “garbage disposer” in the cell membrane bearing some resemblance to the rotating motor ATP synthase has been described in Nature.1  This machine, called AcrB, expels toxins from the cytoplasm through the cell membrane to the outside.  Like ATP synthase, it has three active sites at one end where the binding occurs, and it operates on proton motive force; but unlike the former, it performs “functional rotation” instead of mechanical rotation.    Murukami et al., a team of five in Japan, described the machine in the 14 Sept issue of Nature.1  Here is a simplified picture of how it works.  Picture a pie with three slices and follow a toxin from the inside of the cell, through the AcrB disposer, to the outside.  One of the slices has a port open and ready for use; we follow the molecule inside as it gets dragged in because of the proton flow.  A trap door lets us into the first chamber then snaps shut.  Inside, we are squeezed into another chamber, then into a tunnel, then handed off to a membrane protein that ejects us out to the exterior environment.  The squeezing occurred because the neighboring pie slice opened its port when ours closed.  When the third slice opened in turn, we were ejected into the tunnel.  In this “functional rotation” model of the action, each of the three segments cycles through three states, and affects the state of the neighboring segment.  The result is a continuous garbage-disposer like operation that sucks in the toxins, binds them, and ejects them out.  Apparently each segment can handle a wide variety of substrates, and adjacent segments might be working on different molecules simultaneously.    There’s one bad side effect of this technology for us humans.  For doctors trying to administer chemotherapeutic drugs or antibacterial agents, the bacteria put up a challenge; they can be ejecting the drugs as fast as the doctor administers them.  This is one way bacteria gain immunity to drugs.  Finding ways to disable these “ubiquitous membrane proteins” may be easier now that we know how they work.  This particular machine operates in the lab bacterium E. coli, but there are other types of these “multi-drug transporters” (MDTs) in other organisms that work in other ways.  In the same issue of Nature,2 two Swiss researchers described a different MDT in S. aureus called Sav1866.  Instead of proton motive force, this member of the ABC family of MDTs uses ATP to twist the toxin out of the membrane.    In the case of the rotary machine AcrB, both the research team and commentator Shimon Schuldiner (Hebrew U) couldn’t help but notice the resemblance to ATP synthase.  AcrB lacks the mechanical rotation of the gamma subunit, and seems to lack the rotating carousel driven by protons, but it does have three active sites that appear to operate in turn like a rotary engine.  Schuldiner did not explain any details of a relationship, but speculated that AcrB might be a missing link of sorts: “It is possible that this is a remnant of the evolutionary process that led to the development of true rotary molecular machines.”  Other than that, and an offhand remark earlier in the commentary that “MDTs have evolved into many different forms to act on a wide range of xenobiotics” [i.e., alien molecules], the only other reference to evolution in any of these three papers was a speculation about Sav1866 by Dawson and Locher.  Noting the functional similarity but distinctly different architecture between Sav1866 and another member of the ABC family of MDTs, “the bacterial lipid flippase MsbA” in Salmonella, they cannot see an evolutionary relationship between them: “The observed architectures of MsbA and Sav1866 remain incompatible, even when considering that the proteins may have been trapped in distinct states,” they note.  So what is the answer?  How did these structurally different yet functionally similar machines originate?  They leave it at, “the differences—if real—would indicate a convergent evolution of the two proteins.”1Murukami et al., “Crystal structures of a multidrug transporter reveal a functionally rotating mechanism,” Nature 443, 173-179(14 September 2006) | doi:10.1038/nature05076.2Dawson and Locher, “Structure of a bacterial multidrug ABC transporter,” Nature 443, 180-185(14 September 2006) | doi:10.1038/nature05155.3Shimon Schuldiner, “Structural biology: The ins and outs of drug transport,” NatureIt’s important for us to keep reporting what biophysicists and biochemists are finding, so that the Darwinists know what they are up against.  The cheap calls of “convergent evolution” and “remnants of the evolutionary process” and other such calls to accept evolution as an assumption are ringing hollow, and need to be ejected with the rest of today’s intellectual garbage and toxins.(Visited 23 times, 1 visits today)FacebookTwitterPinterestSave分享0last_img

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