Views of integrase

HIV integrase (the recent molecule of the month) is known from its close structural kin.  The following is the abstract of the recent “putting it all together” article that appeared in the scientific journal Nucleic Acids Research (2009 by Cherepanov and colleagues):

“Establishment of the stable provirus is an essential step in retroviral replication, orchestrated by integrase (IN), a virus-derived enzyme. Until now, available structural information was limited to the INs of human immunodeficiency virus type 1 (HIV-1), avian sarcoma virus (ASV) and their close orthologs from the Lentivirus and Alpharetrovirus genera. Here, we characterized the in vitro activity of the prototype foamy virus (PFV) IN from the Spumavirus genus and determined the three-dimensional structure of its catalytic core domain (CCD). Recombinant PFV IN displayed robust and almost exclusively concerted integration activity in vitro utilizing donor DNA substrates as short as 16 bp, underscoring its significance as a model for detailed structural studies. Comparison of the HIV-1, ASV and PFV CCD structures highlighted both conserved as well as unique structural features such as organization of the active site and the putative host factor binding face. Despite possessing very limited sequence identity to its HIV counterpart, PFV IN was sensitive to HIV IN strand transfer inhibitors, suggesting that this class of inhibitors target the most conserved features of retroviral IN-DNA complexes.”

Now here’s a question for an artist:  How much of the so-called PFV complex (structure 3os1 in the PDB) should be portrayed?  The whole complex is exceedingly, well, complex!

The central subject
Here is a view showing just the A chains of 30s1 (without the multiple DNA strands that intertwine in the hole in the middle):

The outlying objects

Here are the B chains of 30s1.  (They lie on the outskirts of the above A chains which I’ve now made invisible:

Resemblance to other objects

Now here is the so-called “core integrase” that crops up when you search for “integrase” in the PDB (e.g. this is one of the chains you’ll see in the core integrase of structure 2×78):

The “core” integrase is essentially the same structure as the B chains that lies on the outskirts of the main complex.  You would think that a “core” is essential, and perhaps it is from a strictly scientific viewpoint, but perhaps not from the artistic viewpoint.  As an artist, we often choose to ignore the peripheral elements of a subject … we portray the face, not the torso … the flowers and vase, not the table legs (well, Cezanne paid close attention to the table legs, but I digress).

Sometimes less is more

Art is an expression.  Feel free to leave out portions of a complicated structure if it doesn’t excite your creativity.  Let your eye choose your subject. If scientific detail (important detail no doubt) gets in your way, trim it away as mere artistic clutter!  Here’s the whole integrase complex (magenta = A chains, azure = B chains, gray = DNA strands) … trim as necessary!

This entry was posted in Student posts. Bookmark the permalink.

Leave a Reply