 One of the parts I love with membrane proteins is how both their formation and function are quite physical despite the extremely biological processes. Don Engelman, who was one half of that Popo Engelman model, came out with another very interesting result. He started a protein called glycophorin A, which actually consists of a single helix. And this helix, when you put it in a membrane, turns out that it form helical pairs. There's even an NMR structure of it here. Do you see how they cross each other at an angle? We already talked about that for globular proteins, that it's frequently advantages for proteins to cross alpha helices to form this angle so that the ridges will fit into the valleys of the other helix. But Don Engelman found something else that is very common in the sequences to find a pattern that you had some sort of amino acids and then you had a glycine. Then you have three other amino acids, X with no amino acids, and then we had a glycine again. So that's a case called the GX3G motif. Motif is pattern. If you know your alpha helices, which you do by now because you've studied them in great detail in the last few lectures, right? Just draw that glycine, draw the three Xs and draw the second glycine. That's going to mean that the two glycines show up on the same side, roughly the same side of the helix, because we have 3.6 residues per turn, right? What is the size of the glycine side chain? Well, there is no glycine side chain. So glycine will not really have one of those ridges. And if you not put two glycines next to each other, that's going to be like a helix, but it's almost a depression on it. If we have two helices that I would like to pack against each other, it's a great idea to have a depression on one helix and a depression on the other helix, because that will make them get even closer. So that's going to be a beautiful packing pattern that will make sure that the helices can pack. This was a remarkable result. Don showed with a whole set of experiments that you can mutate this. You can get certain amino acids to stabilize these by forming additional hydrogen bond interactions or so. And part of this enthusiasm was that when we found this, we thought that we are now starting to find all the motifs that will explain how membrane protein helices pack. The only problem is that we haven't really found any more motifs like this. So I'm not going to say that it was a sidetrack. This is an important motif and you do find it where helices need to pack, but we haven't really been able to generalize this. It's not just a simple packing of one helix against another, but it turns out that membrane protein packing is at least as complicated as globular protein packing. In particular, as we have larger and larger membrane proteins now that are not just simple parallel helices. And I think it's a great example that this seemingly simple model that membrane proteins are kind of the opposite of globular proteins or that it's just a matter of simple helix packing. Well, it turned out not to be quite that easy, which is great because that means that people like I still have a job.