Field of Science

Translocon structure

Well, I'm still busy with revision but, miraculously, I seem to have almost achieved my crazy aim of writing all of first terms lectures notes in a week *dies theatrically*. I still don't actually know any of the stuff, but at least I now have notes to work from, and I understand it all, which is important.

Topic of the day today was protein targeting within cells, specifically targeting secreted proteins to the inside of the endoplasmic reticulum; a network of internal membranes which modifies secreted proteins and then exports them out of the cell.

Best story in all this is about the discovery of the structure of the translocon; the channel the protein goes through to get into the endoplasmic reticulum (through a membrane). When they first started looking at the structure of the translocon, they saw it was usually found in the form of four proteins very close together, so the first idea was that these formed a ring, with a nice wide hole in the centre for the protein to travel down. It made sense; but unfortunately it only made sense in that specific biological way where the idea is nice but it doesn't fit in with biology.

Because from the cells point of view (if it has one) a large channel like that is a very unhelpful thing to create. You can't regulate it; it needs a filter, or a cap, or some mechanism to prevent just anything going through. Also, a closer look at the translocon showed that it wasn't always found with four proteins close together; sometimes there were three, or two, which would make the channel even less specific or (in the case of only two) almost non-existent.

So the current model (with a lot more supporting evidence) is that there is a little channel down the middle of each individual protein, shaped a bit like an hourglass, which secreted proteins travel through to enter the endoplasmic reticulum. This model works better, especially as the middle bit of the hourglass can expand and change shape; allowing protein folding inside the channel. This also allows for proteins that want to stay in the membrane to be released, there's a little exit space near the middle of the hourglass (alpha helix two of Sec61 for those who are interested) that allows the protein to escape from the translocon into the membrane before it enters the endoplasmic reticulum.

But of course every new model leaves questions behind that were answered by the old model. The thing now, is nobody is quite sure why the proteins cluster together in groups of (mostly) four. If they have a channel through each protein, why not be all separate? Why form specifically numbered groups? It has been suggested that one protein is used for recognition while the other is actually used for the channel but it's all a bit uncertain at the moment.

*sigh* I miss lab work. I miss blogging about lab work. Revision is like forcing yourself to eat when you're already full, I want to get onto some new stuff.


BiochemGirl said...

I'm enjoying your revision-related posts because reading them makes me feel like I'm revising :P. I'm doing basically the same stuff in molecular biology at the moment... a pity because the things I really need to learn are actually in microbiology. Still, you've given me an idea: maybe I can better remember some of this stuff by trying to explain it to others?

Lab Rat said...

Glad it was helpful! I prefer blogging about lab work myself because it's all new and interesting, but I can get some microbiology posts up if that's what your revising. Explaining to others definately helps, it sort of organises things in your head in a much better wayy than just thinking about them.

Write a blog post about it! I would be interested to read it.

Anonymous said...

I’m not sure that’s right. Separate proteins don’t form separate pores. The sec61 complex is made up by the alpha subunit that spans the membrane 10 times and is split into two (tm 1-5 and (tm 6-10) held together by the gamma subunit. The transmembrane segments 2 and 7 help clamp the signal sequence of the nascent protein. Initiation of co translation-translocation begins, with the isolucine rich constriction forming the hourglass shape clamps the protein to stop leakage. The signal peptidase associated with the translocon is thought to be helped by 4 copies of the alpha sub unit also associating with the translocon, cleaves the peptide and voila! translocation. So, there is only one pore...that’s why they associate, not separate pores formed by the subunits, that I think you have insinuated.



Lab Rat said...

Charlene: What I was trying to say was that the translocation happens down the middle of one Sec61 complex, rather than in a pore formed by three of them, as was previously thought (and previously taught to us, two years ago). Which as far as I'm aware is mostly correct, and seems to be what you are saying as well. I probably should have been clearer with using the term 'subunit' there.

Thanks for the extra information!