Even Your Trash Can Is High-Tech
Cells have the same problem as cities: disposing of trash. Each of your cells has elaborate trash collector machines that not only dispose of damaged or unneeded proteins – they recycle them, too. The structure of the proteasome, a fragile machine difficult to crystallize for imaging, has just become clearer thanks to researchers in Germany and Switzerland who reported their findings in PNAS.1 Here are some of the details of what happens:
Unlike constitutively active proteases, the proteasome has the capacity to degrade almost any protein, yet it acts with exquisite specificity. The key stratagem is self-compartmentalization: The active sites of the proteolytic 20S core particles (Cps) are sequestered from the cellular environment in the interior of this barrelshaped subcomplex. Proteins destined for degradation are marked by a polyubiquitin chain, a degradation signal that is recognized by the 19S regulatory particles (Rps) that bind to either one or both ends of the CP to form the 26S holocomplex. The Rps (i) recognize the polyubiquitylated substrates, (ii) trim and recycle the polyubiquitin chains, (iii) unfold substrates to be degraded, and (iv) open the gate to the CP and assist in substrate translocation into the interior of the CP. These tasks are performed by a complex machinery involving at least 19 different subunits, 6 AAA-ATPases (Rpt1?6), and 13 non-ATPases (Rpn1?3, Rpn5?13, Rpn15/Sem1p).
In plain English, the barrel-shaped machine recognizes trash by chemical tags that have been put on them. A special lid reads these tags of ubiquitin, takes them off, unfolds the trash protein, opens a special lid, and stuffs it inside, where the innards take the amino acids apart for recycling. This is all done by “complex machinery” with 19 parts, 6 that spend ATP for energy, and 13 that don’t. This machine “has the capacity to degrade almost any protein, yet it acts with exquisite specificity,” they said.
Their model image of the 26S proteasome looks a bit like one of those old PEZ candy dispensers, with a hinged lid, only much more elaborate. From the top, the lid looks like a six-sided spiral. All around this lid are functioning parts: a protein that recognizes the ubiquitin tag, another complex that takes the tags off for recycling, parts that open the lid, parts that pull the trash inside, and then the core complex (barrel) where the degradation takes place. What happens inside remains a mystery. They said that some parts undergo large conformational changes (moving parts) during operation, and some portions are “highly conserved” (unevolved) in eukaryotes. The authors said nothing about evolution.
As is common these days, the authors spoke of this system as “machinery”. Some evolutionists complain about the machine language, claiming it is “unfortunate and misleading.” David Tyler addressed this issue on Uncommon Descent, asking, “Are machine-information metaphors bad for science?”
1. Bohn, Beck et al, “Structure of the 26S proteasome from Schizosaccharomyces pombe at subnanometer resolution,” Proceedings of the National Academy of Sciences published online before print November 22, 2010, doi: 10.1073/pnas.1015530107.
Your cells go green! They have recycle barrels just like the ones you put on the street, except these are motorized, pull the trash inside, and do the recycling on the spot. They don’t let in good proteins, because the quality-control system has put special tags on the trash that the proteasome has to read before acting on it. It’s all part of an elaborate recycling system.
Evolutionary theory was useless to this discovery, just like it is to every careful inspection of the details of cellular machinery. “In eukaryotic cells, most proteins in the cytosol and the nucleus are regulated via the ubiquitin-proteasome pathway and malfunctions of this pathway have been implicated in a wide variety of diseases,” the authors said. My, wonder how life got along before Tinker Bell came up with this series of mutations, enough to build 19 exquisite protein parts working together as a system, when getting just one usable protein is astronomically improbable (see online book).