NalP: Difference between revisions

Neisseria meningitides is a bacterium that infects humans and is the leading cause of “Meningitis (inflammation of the membranes surrounding the brain and spinal cord) is a common form of meningococcal disease and is characterized by fever, severe headache, and stiff neck. Patients with meningococcal sepsis (severe illness caused by bacteria or their toxins in the blood) may present with high fever, hypotension (low blood pressure), and profound weakness. In either case, patients may develop a characteristic rash including petechiae (pinpoint red spots that do not blanch with pressure) or purpura (purple areas similar to bruises) that are caused by bleeding into the skin. Purpura fulminans (hemorrhagic condition resulting in tissue necrosis and small vessel thrombosis) can result in scarring or limb amputations. Approximately 10-14% of cases of meningococcal disease are fatal. Of patients who recover, 11-19% have permanent hearing loss, mental retardation, loss of limbs or other severe sequelae.” <http://health.state.ga.us/epi/bacterial/path-neisseria.asp> For this reason major amounts of research is being done on this bacteria and its transport mechanisms.

The unique structure that makes this pore is able to allow for transportation in and out of the gram-negative cell is what is called a beta barrel. 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, T0, connects the alpha-helix to the N-terminal beta strand.  The alpha helix has its N-terminus side facing outward toward extracellular material.

Recent research has showed that there are possible conserved features to this pore and pores in other types of gram-negative bacteria. Autotransporters that also have the conserved structure of an alpha helix directly preceding the beta core include: AidaI of E. coli, BrkA of B. pertussis, Hap of Hemophilus influenzae and IgA protease and App of N. meningitidis. Much of the these proteins show low conservation within their alpha helixes yet they all have a long traversing alpha helix that leads into the 12 sheeted beta barrel. Due to the amount of research being done on the Neisseria meningitidis' NalPβ protein, its crystal structure is being used in order to model autotransporter secreti