When it rains it Cascades

This week saw not one, but two papers with structures of the E. coli Cascade complex from the labs of Yanli Wang (Nature) and Scott Bailey (Science). Cascade is a bit like Cas9, in that it’s a bacterial immunity endonuclease targeted via CRISPR nucleic acid, but far more complex. While Cas9 is a single protein (and hence attractive for genome engineering), Cascade is 405 kDa split over 11 separate polypeptides and 5 open reading frames. In both structures, the crRNA is stretched out across the entire complex. The structure from Bailey’s group also has ssDNA bound, and while it generally follows the path of the crRNA, kinking and base flipping allows the pairing to severely underwind into a ribbon. As is often the case in a large, complex structure like this, there are all kinds of exciting bits to poke into and look at to explain existing biochemical data. I’m looking forward to carefully reading both papers and playing with the structures when they’re released. Kudos to both groups!

On a side note, these are huge ~ 3 A structures that also contain nucleic acid, yet both are refined to levels that would have been unthinkable just a few years ago: R/Rfrees of 22.5/29.9 and 20.7/16.4! Of course there’s more to structure quality (and a structure) than the R-stats. But still, it’s astounding.