 So in the early days of studying protein biogenesis, when Gunnar von Hainer, for instance, proposed a positive inside rule, another group studying helices was Don Engelman. And Don Engelman studied a very simple helix called glycophorin, glycophorin A. This is a single-spanning membrane protein that is an individual helix that just goes straight through the membrane, fairly hydrophobic and boring from that point of view. The interesting thing with glycophorin is that it has a very peculiar pattern, a motif in the amino acid sequence. And that means that you have pretty much any amino acids, and then you must have a glycine, and then you can have three other amino acids, but it has to be exactly three, and then you must have a glycine again, and then the chain continues. It turns out that this forms an alpha helix. If you know something about the alpha helix, how many residues are there per turn in a typical alpha helix? 3.6. So in practice, these two glycines are going to be roughly on the same side of an alpha helix. You can also show in experiments that these alpha helices would actually form dimers and membranes. And here the beauty is that if I have one alpha helix here, and one alpha helix here, and I would like them to interact, the problem is that there are side chains, and there are side chains in the way, right? I will bump into my peer partner side chains here, unless they are glycines. The glycine will effectively, if I try to draw a helix here just in sort of space filling fashion, this will almost create a depression on the side of that helix. Similarly for this other helix, there will almost be a depression on the side of that helix too. And you can imagine what now happens if I push these helices together, right? These depressions will fit each other, and they will form a very nice stable dimer. You can see that if you make an NMR experiment. So here's an example of an NMR structure of glycophorin A. And this GX3G motif is up here. So either you call it GXXXG or GX3G. The reason why this was a landmark discoverer's first is that when this was published, there was a lot of hope by many people. Me included that maybe this is the first motif, and now we're going to gradually start finding all the motifs and be able to understand membrane protein packing just by finding the motifs. Unfortunately, that has turned out not to be the case. And that's why I mentioned to you earlier that membrane protein packing and structure stabilization is much more complicated than we think. There are pretty much no other motifs. But for the glycophorin helices, we found something else. What if some of these X residues here, or at least residues close to the GX here, what if they are serins or threonins? So they're not charged, so I can introduce them in the membrane. But if I now have one serine here and one serine here, they can start to form hydrogen bonds with each other. So the hydrogen on this serine will interact with the oxygen on that other serine. So sure, introducing the serins per se in the membrane, that's not going to be good. But both serine, asparatine, and threonine, once I have done that, they're going to create a strong driving effect to dimerize helices so that we make them form hydrogen bonds with each other instead of stealing their partner in the chain. So surprisingly, introducing something that's somewhat polar in the membrane, the first step of introduction is not good. But once you've done that, they can create a strong driving effect that helps stabilize membrane protein structure.