Biological complexity: more cell pore complexity (Introduction)

by David Turell , Wednesday, February 24, 2016, 21:53 (3195 days ago) @ David Turell

Materials must move and out of the nucleus and the cell at high speed. Very lage and complex molecular structures control this process:-http://phys.org/news/2016-02-nuclear-pore-complex-billion-years.html-"The interactome is exactly what it sounds like: any exhaustive set of molecules that can be connected with thin black lines in a figure in a research paper. Practically speaking, this meant starting with a few fluorescently-tagged versions of known core nuclear pore component proteins (called nucleoporins or Nups), and 'walking out' from there using affinity capture and mass spectrometry to identify other proteins that stick.-"While there are plenty of contenders for the title of world's greatest protein complex—the ribosome, proteosome, ATPase, and centromere for example—the NPC may be the mightiest of all. At an undisputed 50 MEGADaltons (124 for the mammalian), the NPC contains about 500 subunits comprised of some 30 different Nups. Rather than splashed together like a respiratory complex, the NPC is carefully assembled into an 8-fold symmetric structure that rivets the double nuclear membrane together. To give some idea of the budget that cells are on, the nucleus might have 2000 NPCs (more if mitosis is coming), each ferrying consumables at a rate of 1000 translocations per second.-"What exactly is a translocation you might ask, and who gets to go in or out? That depends on a lot of things, like that minimum pore size we mentioned above. Although there is no hard and fast size limit to what can pass through by unaided diffusion, things slow down considerably for proteins at around 60kDa. Above that, translocation doesn't become energy dependent per say, but ultimately the ferryman needs to get paid with the hydrolysis of two GTP each time the turnstyle turns. The way it works is neatly described by something known as the Ran-GTP cycle. Many folks are familiar with the idea of gradients across membranes (usually electrical, proton, sodium or other ion), which are harnessed to power auxiliary movements. -"The Ran cycle is said to run on a Ran protein gradient where the concentration of the GTP bound form is high inside. and GDP bound form is low outside the nucleus. The tricky part is biasing the pore to get things moving in the right direction. Ribosomes and mRNAs made in the nucleus need to get out, while nuclear proteins translated in the cytoplasm need to get in. These affairs are all neatly enforced by an expansive array of adapters which recognize and bind canonical nucleic acid cytoplasmic localization sequences on the former, and amino acid nuclear localization sequences on the later.-***-"Among the critical conserved components that the researchers in all eukaryote NUPs were the major protein folds on the core scaffold Nups lining the main pore. The Nups form the two inner rings which are in turn sandwiched between two outer rings. They contain folds known as ?-solenoids and ?-barrels or propellers. The importance of these folds is increasingly appreciated as they continue be found at the heart of many newly determined protein crystal structures. The mitochondrial Tom and Sam translocases have them, as do various vesicle coat proteins, including clathrin/adaptin, COPI, and COPII proteins. The authors note that these proteins share architectural characteristics with outer ring Nups, and hint at a common ancestry between the endomembrane trafficking system and the NPC. This so-called 'proto-coatomer hypothesis' further suggests that key components of the cell's secretory system took origin by virtue of their ability to bend membranes, a key first step in the assembly of the pore."-Comment: A highly complex set of structures for pores in the nucleus, the mitochondria and the cell wall. How did evolution find this when it was needed to be invented? Obviously requires planning to get it right. Only mentation can do this. Look at the diagram.