So much for me keeping a blog. I had final exams, and friends’ graduation. I was busy… But enough excuses.
Today, I present to you Hsp90.
This protein is one of the best conserved proteins - it is present in E. Coli, yeast, C. elegans, and yes, of course, mice and even humans. This protein helps other proteins to fold, and when they misfold, it can help them go right again.
Hsp stands for Heat Shock Protein. There are many of these, and they are all quite important. Hsp90 is kind of unique though. Whereas other Hsps bind to specific sequences (some bind to nascent polypeptide chains, others bind to short apolar motifs, etc…), nobody has yet determined how Hsp90 chooses its targets, or where it binds.
Now let’s go a little bit into the structural biology of this protein. It has three domains, the N-terminal domain (NTD), the Middle Domain (MD), and the Carboxy-terminal domain (CTD). The NTD is what binds ATP — the bright spheres in the above image. The CTD is the really dense region at the rightmost end of the protein - its function is to bind to another CTD: If you look really closely, you’ll see the image above has a line of symmetry. This is because the protein I’m showing you is in its dimer form, which means that it is bound to itself. Thus, there are actually two polypeptide chains in the image above that are actually the same. When the chain binds to ATP, it is in the closed conformation. Once the ATP is converted to ADP, the chains actually open, kind of like a scissor, where the handle would be the CTD. Somehow, this motion must help the folding proteins (called clients) to find the correct conformation. How? Nobody knows (but I will be researching this at MIT this summer!!!).