Welcome back to another week of “This week on the PDB”, where I discuss you a very small section of new, never-before-seen protein structures uploaded to the Protein Data Bank, because proteins just keep on getting discovered.
- Lysozyme is an enzyme essential to our immune system that destroys bacterial cell walls. It is ubiquitous in the body: tears, mucus, blood, you name it, you can probably find lysozyme there. Lysozyme also holds a special place in the PDB, as not only was it the FIRST structure to be deposited in the PDB, back in the day when the whole PDB consisted of only 7 structures, but it is also the protein with the MOST different structures deposited, largely owing to a series of experiments conducted Brian Matthews where he made various (and by “various”, I mean “hundreds of”) mutations to lysozyme. Lysozyme is also one of the most consistently crystallisable proteins and has consequently been used to study the protein crystallization process. This week, lysozyme has once again reared its head on the PDB, where Hosur et al. deposited four new structures of lysozyme, at different time increments in the guanidine hydrochloride and glycerol soaking process. The picture below is of the four structures and the ligands aligned with each other. The PDB accession codes are 5H6A, 5H6C, 5H6D, and 5H6E. The associated article has not been published yet, so it the purpose of this structure is unclear, but be sure to check out all the other hundreds of lysozyme structures on the PDB, which can be accessed here.
Hen Egg White Lysozyme native crystals soaked in precipitant solution containing 2.5 M guanidine hydrochloride and 25% glycerol. - PolyA polymerase module of the cleavage and polyadenylation factor (CPF) from Saccharomyces cerevisiae. In order for a freshly transcribed piece of RNA to mature into a useful piece of mRNA for translation, its 3’ end must be cleaved, and a string of adenines added to form a polyA tail. CFP mediates this whole process, making it one of the MVPs of mRNA processing, but for some reason, we don’t really know how this amazing complex of proteins so important to our existence assembles itself (shocking, I know. I rank it high in my list of “why don’t we know this” along with the polymerases involved in DNA replication, where there has been ambiguity for quite some time now). At least, until Casañal and Kumar et al. solved the structure of nuclease, polymerase, and phosphatase modules of the CPF in the common baker’s yeast, S. cerevisiae, using electron microscopy with a resolution of 3.55Å. You can read all about the structural features, such as the four beta propellers (ooooohhh), of the yeast—a great model eukaryote—CPF here. The PDB accession code is 6EOJ.
Cleavage and polyadenylation factor (CPF) from Saccharomyces cerevisiae - Crystal Structure of pro-TGF-beta 1. This structure of the pro-transforming growth factor-beta 1 from the wild boar was obtained through x-ray diffraction by Zhao, B., Xu, S., Dong, X., Lu, C., Springer, T.A. with a resolution of 2.9Å. TGF-beta 1 mediates many cellular functions, including growth, division and proliferation, differentiation, and apoptosis (programmed cell death). It is also important for the immune system, where it can interfere with other cytokines involved in the cellular immune response. In general, it is a very important cellular signalling protein, specifically a cytokine. It also has an implication with tumor development, and consequently holds relevance to cancer (as we all know, anything with connection to cancer is a hotbed of potential biomedical research). This structure has a swap between the N-terminal prodomain and the C-terminal GF domain, which appears to affect how the proteins assemble with each other. The associated article is heavy on the structural biology and lighter in clinical implications, but can be read here. The PDB accession code is 5VQF.
The previous week, a total of 220 structures were released on the PDB. While many of them were simply different resolutions of the same protein (not to mention those four lysozyme structures), there are still a plethora of structures released every week. This just goes to show the expansiveness and diversity in the realm of macromolecules. You can find all the PDB releases this week here: https://www.rcsb.org/pdb/results/results.do?tabtoshow=Current&qrid=5DCB7136. See you next week!
The Abstract 