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Suraj Prakash Sharma | Ekta Chotia


2.5.         Aquaporins

These are the transmembrane proteins with six right handed α helices, there carboxy-terminal and amino terminal both are facing towards cytoplasm and both halves seems to be tandem repeats regarding their amino residue sequence.

There are also five inter helical loops regions among six α helices (A, B, C, D, E respectively), among all these loop B and E having a highly conserved Asparginine, Proline, Alanine (NPA) motif, which forms a 3-D hour glass like structure in the membrane that facilitate the water transport and a comparatively small selectivity filter (R-filter).

Aquaporins are usually found in the plasma membrane as a tetramer, where each tetramer works as an independent water channel. The NPA motif of Aquaporins generates a local electric field in the channel wall, making water molecules to orient in a manner, that the hydrogen atom of water molecule facing the Asp of NPA motif and they invert their orientation in the mid of the motif facing with the oxygen atom up.

The arginine (R) selectivity filter helps the NPA motif to bind to only H2O molecules and excluding others because it is the narrowest part of the pore. The filter also acts as proton filter that is quite necessary for proper functioning of aquaporins regarding the electric field of NPA motif. Kidney is the major abundance site for aquaporins hence they are regulated by anti diuretic hormone (vasopressin). Some mammalian aquaporins are compared in the table given below:

There are five homologous subfamilies of aquaporins have been identified in plants also

  1. PIP – Plasma membrane Intrinsic Protein
  2. TIP ¬–Tonoplast Intrinsic Protein
  3. NIP –Nodulin-26 like Intrinsic Protein
  4. SIP –Small basic Intrinsic Protein
  5. XIP –X Intrinsic Protein

All the members of these aquaporin sub families serve to facilitate the transcellular symplastic pathway of water transport among the plant species. The mercuric chloride is a potent inhibitor of aquaporins. 

2.6.         Pore forming toxins (PFT’S)

Some bacteria like Clostridium septicum and Staphylococcus aureus produce proteotoxins that makes  numerous unregulated  pores in the membrane of the targeted cells to kill them.

These pore forming toxins are classified into the sub categories as shown in the given table:

β–Pore forming toxins are dimorphic proteins mostly made up of β–strands based domains that are soluble monomers and assemble to form the pore. Such pore disrupts the regulated gradient of ions and small molecules of cytoplasm and allowing continues outflow along with nucleotides and amino acids. They also facilitate the excess diffusion of water into the cell that leads to blebbing (swelling) and finally to the cell death because of burst.

Binary toxins consists of, component A (an enzymatic component) and component B (a membrane altering component). The component B forms homo oligomeric pores that facilitate the entry of component A to the cytosol where it inhibits the following normal cell processes.

  • Polymerisation of G-actin to F-actin by mono ADP-ribosylation at arginine 177 of G-actin leading to cell death.
  • Zinc-metalloprotease of component A interferes with the MAPKK signalling and making the cell insensitive to extracellular stimuli.
  • Increase the Ca+2 influx and rises the intracellular cAMP levels that blocks the leukocyte proliferation, phagocytosis and release of porin inflammatory cytokines.

2.7.         Ionophores

These are the hydrophobic molecules produced by microorganisms that facilitate the ion transport across the lipid bilayer of the cell membrane. There are two categories of ionophores are

  1.  Carriers compounds: These are the mobile ion carriers that facilitates the transport of  ions through the  lipid membranes by masking their charge. 
  2. Channel formers: These ionophores make a hydrophilic pore in the lipid bilayer that allows the ion transport by avoiding their contact with lipid bilayer.

These molecules simply works as an antibiotics and disrupts the ion gradient that is necessary for normal cell functioning. This is a potent act of defence among microbes with their competitors. Many ionophores shows very strong affinities for Na+ and K+   like macrolides.

2.7.1.     Ionophores for Ca+2

A23187 (calcimysin) : This antibiotic is produced during fermentation by Streptomyces. It acts as ionophores for divalent cations like Ca+2, Mn+2, Ba+2, Mg+2, Sr+2. It also uncouples of mitochondrial ATP synthesis activity and used in In Vitro Fertilization (IVF) as a potent Ca+2 ionophores.

Beauvericin: It is the depsipeptide isolated from fungus Beauveria bassiana. It is also produced by other fungus having antibiotic and insecticide effects. It acts as an ionophore for alkali metal ions.

Ionomycin is also a Ca+2 ionophore used  to increase the inner Ca+2 levels for the production of cytokines like interferon, perforin, IL-2, and IL-4 that has a significant inflammatory response. These are produced by a bacterium, Streptomyces conglobatus.

2.7.2.     Ionophores for Na+

Monensin A is an ionophore for monovalent cations like Li+, Na+, K+, Ag+ and also has crucial role as an Na+/H+ antiporter. It exhibits antibiotic, antimalarial and inhibits protein transport. It is a polyether isolated from Streptomyces cinnamonensis.

Gramicidin A is also a monovalent (Na+ & K+) ionophore obtained from the soil bacterial species Bacillus brevis, used to induce hemolysis in lower concentrations than bacteria cell death. It is active against Gram positive and some Gram negative bacteria.

2.7.3.     Ionophores for K+

Valinomycin is natural neutral ionophore obtained from Streptomyces tsusimaensis and Streptomyces fulvissimus. It is a dodecadepsipeptide highly selective for K+ ion over Na+ within the membrane. The value of stability constant K with these ions are 106 and 10 respectively. It consists twelve alternate amino acid residues and esters that creates its affinity for metal ions and responsible for salvation in polar solvents. Recently Valinomycin is suggested as a potent agent against SARS corona virus, which is responsible for severe acute respiratory syndromes.

Nigericin is also a monensin like antibiotic produced by Streptomyces hygroscopicus but commercially it is obtained during fermentation of geldanamycin, as a byproduct. It is also named as Antibiotic K178/X-464, Helixin C, Azalomycin M or Polyetherin A. Both salinomycin and gramicidin are the antibiotics that also work as K+ ionophores.

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