Tuesday, May 01, 2012

On the shore

The illustration above is from an article in the 12 April issue of Nature called “Structure of the mitotic checkpoint complex,” by a research group at the Institute of Cancer Research in London. It is typical of diagrams one sees with increasing frequency in the scientific journals.

I have only a foggy idea of what’s being represented. Here is the abstract of the article:
In mitosis, the spindle assembly checkpoint (SAC) ensures genome stability by delaying chromosome segregation until all sister chromatids have achieved bipolar attachment to the mitotic spindle. The SAC is imposed by the mitotic checkpoint complex (MCC), whose assembly is catalysed by unattached chromosomes and which binds and inhibits the anaphase-promoting complex/cyclosome (APC/C), the E3 ubiquitin ligase that initiates chromosome segregation. Here, using the crystal structure of Schizosaccharomyces pombe MCC (a complex of mitotic spindle assembly checkpoint proteins Mad2, Mad3 and APC/C co-activator protein Cdc20), we reveal the molecular basis of MCC-mediated APC/C inhibition and the regulation of MCC assembly. The MCC inhibits the APC/C by obstructing degron recognition sites on Cdc20 (the substrate recruitment subunit of the APC/C) and displacing Cdc20 to disrupt formation of a bipartite D-box receptor with the APC/C subunit Apc10. Mad2, in the closed conformation (C-Mad2), stabilizes the complex by optimally positioning the Mad3 KEN-box degron to bind Cdc20. Mad3 and p31comet (also known as MAD2L1-binding protein) compete for the same C-Mad2 interface, which explains how p31comet disrupts MCC assembly to antagonize the SAC. This study shows how APC/C inhibition is coupled to degron recognition by co-activators.
Yeah, OK.

In that long paragraph I basically recognize one word: mitosis, the separation of the chromosomes in a eukaryotic cell into two identical sets in preparation for cell division, one of the most fundamental processes of life. The diagram above shows in schematic form some of the exquisite molecular machinery that makes this happen.

Back when I was teaching general studies science, I occasionally encountered students who protested, “Science takes all the mystery out of life.” It is, in fact, a fairly common assertion from people who take a perverse pride in not knowing any science.

I look at a diagram like the one above –- and there are dozens in almost any issue of Science or Nature –- and my jaw drops. First, that we have learned enough to describe in such detail processes that are taking place on a scale too small to observe with the naked eye –- all of this is going on in the nucleus of a cell that is 100 times smaller than the period at the end of this sentence. And second, that this astonishing chemical dance happens every time a eukaryotic cell divides. It is happening now, in countless cells of my body, as I type.

If that’s not mystery enough for you, I don’t know what is.

It’s the old image I’ve used before. Knowledge is an island in a sea of mystery. The growth of the island does not diminish the sea, which is effectively (if not actually) infinite. What it does is extend the shoreline where we encounter mystery. Each week I peruse the diagrams in the science journals. I may not understand most of what is being described, but I know when I’m in the presence of something that deserves my attention, awe, respect and praise.