Why is that important? Usher is a membrane part of two component system responsible for assembly and transport of fimbriae/pili in gram-negative bacteria – pretty essential element in these organisms. This protein was identified in early 90s (or even earlier) and for quite a while lots of people tried to solve/predict/model its structure. Its structure was assumed to resemble porin – but a large insert right in the middle of beta-barrel gave lots of problems in predicting correct topology. Now we know (at least my colleague saw it, we need to wait) how the final structure looks like and I was also told that its functional aspects have a big relevance to other secretion systems. Have a look on this protein when it’s out (I’ll post definitely about it) – I think you will be surprised even if nuances of host-pathogen interactions are not very appealing to you.

Studying any niche area on the molecular level can be very rewarding. Novel protein fold by itself is not a big deal anymore (it used to be – browse through archives of Nat. Struc. Biol. from several years ago). But putting this novel structure in well known functional context and understanding constrains that led to a new solution is still considered a first-class science.

This post starts a series devoted to imaginary nanodevices made of proteins. I’m going to play around with known protein structures to see if some of them can form an interesting arrangement. Basic requirement is lack of obvious sterical clashes at the level of a main chain trace. If that is fulfilled I would assume very slight chance that particular arrangement is possible. However, in most cases I won’t bother inventing how to recreate it in the lab, since I don’t feel competent enough. The whole series is more fiction than science and my goal is mainly stretching my and readers imagination.

Lets start with something simple. Structure depicted above is a dimer of leucin rich repeat (LRR) protein (PDB: 1A4Y, chains A and D) with a trimeric coiled-coil (my own model made with BeammotifCC) fitted in. The opening is wide enough to accommodate three helices without any problems. Picture below shows main chain trace of the coiled-coil (in red) surrounded by LRR dimer (all atoms, blue and sea green). As you can see, any coiled-coil made of aminoacids with small side chains would not create any sterical issues. In fact, approximate size of the opening (~35 Angstroms) is much larger than the opening size of the membrane anchor of trimeric autotransporter adhesins (twelve stranded beta-barrel, PDB: 2GR7), which also accommodates a trimeric coiled-coil. So why not to use a beta-barrel instead of LRR? Well, beta-barrels are hardly present outside membranes .

One can ask question if the single LRR protein can make a full ring. It looks possible from the structure of the single repeat (beta-turn-alpha) – interactions with preceding and following repeats are virtually the same. However, secondary structure elements of these repeats are not perfectly aligned with the axis of the opening. Their tilt forces consecutive repeats to form an imaginary spiral, not a circle (although the tilt does not seem to be large enough to actually allow for spiral folding of larger number of repeats – but that’s only my assumption, it would be worth to check).

So that’s it for now. If you feel that I’m rediscovering wheel, writing something completely silly, or you have any suggestions, please feel free to discourage/encourage me with comments.