NalP: Difference between revisions

The beta barrel is a unique structure that makes this pore able to allow for transportation in and out of the gram-negative cell. This beta barrel is created with 12 anti-parallel beta-pleated sheets that have wrapped around creating anti-parellel interaction between sheet one and sheet 12. This creates a tube structure that transcends through the membrane of a cell creating a new environment that allows for polar molecules to move through the cell membrane and cell wall when they would have otherwise been stopped by the hydrophobic center of peptidoglycan. The start and end of the beta barrel is on the periplasmic side of the membrane and a short tight turn, <scene name='Translocator_Domain_of_the_Autotransporter_NalP_within_Neisseria_meningitidis/T0/1'>T0</scene>, connects the alpha helix to the N-terminal beta strand.  The alpha helix has its N-terminus side facing outward toward extracellular material. <ref name="PMID: 8254661"> PMID: 8254661 </ref>

Interesting questions were raised on how the alpha helix in the center of the beta barrel affected the mechanism of protein transportation out of the cell. The first step to understanding what shapes of proteins can move though the pore was figured out by trying to move a disulfide bond through the pore. This was unsuccessful and led to part of the understanding that the only way that proteins can move though this pore was by being completely unfolded. Yet once inside of the extracellular material, the protein must be folded. Knowing these two crucial pieces of data, it was clear that as the protein passes through the pore it is folded. Due to the C-terminal end's placement on the periplasmic side of the pore it was highly unlikely that was the participating portion that effected the change in conformation of the protein as it passes through. Oppositely the N-terminal side of the pore lies on the alpha helix facing the extracellular matter, placing it in prime location to change the conformation of the passing protein. Another possible place where interaction could occur between the passing protein and the pore would be at a large hairpin loop that is on the extracellular side of the pore. This would also provide a prime placement for the initiation of protein folding.<ref name="NaIP" />

The Hairpin Model is a much more likely model that could accommodate for the movement across the membrane. The hairpin model allows for a hairpin loop to be created in the passenger protein and as it passes through the end of the pore a hairpin loop there interacts with the passenger protein in order to create the folding. As the protein is folded it provides energy to pull the rest of the protein through. One major problem with this model is the fact that 2 strands must fit through the protein at once and with the alpha helix that is an impossible fit. The model describes a fix to this problem with the destruction of the alpha helix and recreation. When the alpha helix is nonexistent the hydrogen’s that typically face inward and interact with the alpha helix face toward one another or even outward which expands the barrel as well as making it much more flexible.  This model suggests that folding and translocation are interdependent and happen simultaneously.  The problem with this method is there is no mechanism for how the alpha helix is created or dismantled and where it goes.<ref name="NaIP" />

One alternative theory argues that the beta barrel is actually not used as a protein secretion pore at all. As Omp85 compasses the end of the beta barrel it travels toward the cell membrane as if to place the autotransporter into the cell membrane yet instead of placing it, Omp85 continues through into the extracellular material. As the translocator is being carried toward the cell membrane it is able to pick up a passenger protein using its loose C-terminus end that would have faced inward toward the pErIplasm. Then all three the, the Omp85, the translocator, and the passenger protein, are transported to extracellular material through the pore that Omp85 is able to create. Then they all dissociate away from one another, which frees the passenger protein. This is another possibility for how the translocator is able to transport passenger protein out of the cell yet changes the view of the translocator all-together. If this is in fact the way that passenger proteins leave the cell then NaIP is not an autotransporter at all. An autotransporter, just as it sounds, autotransports, meaning that the protein pulls itself through as it is folded on the opposite side of the cell. As plausible as this seems, it would mean a major change in the way that this translocator protein is classified. <ref name="NaIP" />