Welcome back to “This Week on the PDB” for the week of Nov. 7th! This week on the PDB, 133 new structures were released, providing 3D visuals for macromolecules found in species ranging from the common human to the HIV virus. Here are some highlights:
- The solution NMR* structure of the Membrane Associated Segment of HIV-1 gp41 Cytoplasmic Tail was released by Murphy, Samal, Saad, and Vlach. This HIV-1 domain is important in mediating the recruitment and incorporation of the viral envelope protein (Env) into the virion. The full paper can be found in the November 7 issue of Structure, DOI: https://doi.org/10.1016/j.str.2017.09.010. The PDB accession code for this macromolecule is 5VWL.
- Human glutathione s-transferase Mu2 complexed with BDEA in a monoclinic crystal form was released by Zhang et al. The structure was obtained through x-ray crystallography and had a resolution of 1.6 Å. The asymmetric unit consists of two chains, A and B. Glutathione s-transferases (GST) make up a family of proteins that add glutathione to proteins, which aids in their regulation. GST is important in cancer research, and deviations from normal GST structure appears to correlate with increased susceptibility in certain cancers such as lung, prostate, and colorectal. Though glutathione s-transferases (GST) are generally well characterized, and many other GST structures can be found on the PDB, this appears to be the first structure of GST M2. Additionally, this GST is complexed with an inhibitor, and glutathione, giving further insight into how this GST M2 interacts. The article for this structure has yet to be published, but for now you can look at the structure by searching up its PDB accession code, 5HWL.
- Cryo-EM structure of human insulin degrading enzyme was released by Liang et al. The resolution is 6.5 Å and the asymmetric unit contains two chains. Insulin degrading enzyme, as the name suggests, is involved in the degradation of insulin in the cell, as well as IAPP, glucagon, bradykinin, kallidin and other polypeptides, which allows insulin degrading enzyme to affect certain intercellular signalling pathways. Insulin degrading enzyme also breaks down amyloid formed by APP and IAPP, which might have implications in neurology. An article has yet to be published, but for now you can see it on the PDB, with accession code 6B7Y.
- Human Apo-TRPML3 channel at pH 4.8 was released by Zhou, Li, Su et al. The technique used was cryo-electron microscopy and the resolution is at 4.65 Å. TRPML3 channels are mostly found on the endolysosomes and are critical to the endocytic pathway and consequently cell signalling. This apo (unbound) structure at pH 4.8 is very different from the apo structure at the physiological pH of 7.4, and the lower pH appears to inhibit channel activity. Malfunctioning TRPML3 channels can cause deafness and interfere with proper pigmentation in mice, but does not appear to correlate with any human diseases yet. However, malfunction of the closely related TRPML1 channels in humans cause a severe lysosomal storage disease, mucolipidosis type iv. The paper was published November 6 online in Nature Structural & Molecular Biology, and can be found here: https://www.nature.com/articles/nsmb.3502. Its PDB accession code is 6AYG.
This just scratches the surface of this week’s released on the PDB. If you are interested in seeing what the other 129 structures are, you can find them at https://www.rcsb.org/pdb/results/results.do?tabtoshow=Current&qrid=DC1452AE. Happy viewing, and come back next week for more structure releases!
*Solution NMR is a technique where the protein is suspended in a buffered solution and multidimensional nuclear magnetic resonance is applied to the solution. Radioisotope-labelled proteins are also used during the process. Through resonance assignment and by creating different restraints for parameters such as distance and bond angles, a 3D structure can eventually be generated. Solution NMR doesn’t require a crystal to collect data, unlike the case of x-ray crystallography, and also has the added benefit of being able to provide information on the dynamics of the protein, but is limited to small-sized proteins.