Aquaporins

A basic knowledge of aquaporins.
Aquaporin are channel proteins that allow the passive diffusion of water through them.Aquaporins are membrane water channels that play critical roles in controlling the water contents of cells.
These channels are widely distributed in all kingdoms of life, including bacteria, plants, and mammals.
In 2003 Nobel Prize in Chemistry was awarded to Peter Agre "for the discovery of water channels".
More than ten different aquaporin have been found in human body
AQPs can be divided into three subfamilies:
Orthodox or classical aquaporin, considered to be water selective.
Aqua-glyceroporin, permeable to glycerol and other small solutes in addition to water.
S-aquaporin, also called unorthodox super-aquaporin or subcellular aquaporin, a third subfamily only present in animals but not in plants, fungi and bacteria with permeability still uncertain.

1. AQUAPORIN IS A CHANNEL PROTEIN

2. DEFINITION Aquaporins are membrane water channels that play critical roles in controlling the water contents of cells. These channels are widely distributed in all kingdoms of life, including bacteria, plants, and mammals. HISTORY OF AQUAPORINS In 1988, Agre and coworkers isolated a new protein from the RBC membrane and renal proximal tubule membranes  in   Xenopus  oocytes and nick-named CHIP28 (channel-forming integral membrane protein of 28 kDa ). Only in 1992 Agre's group suggested that "it is likely that CHIP28 is a functional unit of membrane water channels“ and were first given the name as Aquaporin-1. In 2003 Nobel Prize in Chemistry was awarded to Peter Agre " for the discovery of water channels", AQUAPORINS

3. IMPORTANCE OF WATER Cell life Chemical and metabolic reactions Transport of nutrients and removal of waste Body temperature regulation As a lubricant.

4. P olar molecule has a net dipole as a result of the opposing charges (i.e. having a partial positive and partial negative charges ) from polar bonds arrange asymmetrically. Water is an example of a polar molecule since it has a slight + ve charge on hydrogen atom and slight – ve charge on the oxygen atom. NEED FOR AN AQUAPORIN WATER IS A POLAR MOLECULE

5. As the diffusion of water molecules through hydrophobic plasma membrane is a very slow process and which is not fast enough to keep our cells alive and to regulate all the essential functions of the body . Therefore we need a channel that could allow a much faster transport of water across membranes relative to lipid bilayer. A single human aquaporin-1 channel facilitates water transport at a rate of roughly 3 billion water molecules per second.  Cont …

6. More than ten different aquaporin have been found in human body AQPs can be divided into three subfamilies : O rthodox or classical aquaporin , considered to be water selective. Aqua- glyceroporin , permeable to glycerol and other small solutes in addition to water. S-aquaporin, also called unorthodox super-aquaporin or subcellular aquaporin, a third subfamily only present in animals but not in plants, fungi and bacteria with permeability still uncertain. TYPES OF AQUAPORINS

7. Aquaporin proteins are composed of a bundle of six  transmembrane   α-helices . They are embedded in the cell membrane. The amino and carboxyl ends face the inside of the cell . Between the helices are five regions (A – E) that loop into or out of the cell membrane, two of them hydrophobic (B, E), with an  asparagine – proline – alanine  ("NPA motif") pattern.  STRUCTURE OF AQUAPORIN

8. The asparagine- prolin -alanine sequences (NPA motifs) are highly conserved in aquaporin water channel family. S tudies of AQP1 structure demonstrated that the two NPA motifs are in the narrow central constriction of the channel, serving to bind water molecules for selective and efficient water passage. Orientation of water molecules moving through the channel assures that only water passes between cells due to the single line passage of molecule. They create a distinctive hourglass shape, making the water channel narrow in the middle and wider at each end . T he oxygen in each water molecule faces forwards as it enters, turning around half way along and leaving with the oxygen facing backwards. Why this rotation occurs is not entirely clear yet. NPA MOTIFS

9. The aromatic/arginine or " ar /R" selectivity filter is a cluster of amino acids that help bind to water molecules and exclude other molecules that may try to enter the pore. It is the mechanism by which the aquaporin is able to selectively bind water molecules (hence allowing them through) and prevent other molecules from entering.  it is typically the tightest part of the channel. Its narrowness weakens the hydrogen bonds between water molecules, enabling the arginine, which carry a positive charge, to interact with the water molecules and to filter out undesirable protons . "AR/R" SELECTIVITY FILTER

10. The most remarkable feature of aquaporin channels is their high selectivity and efficiency on water or glycerol permeation, excluding ions, and protons . Apart from water and glycerol, a number of other permeants (substances which pass though membrane) such as urea, ammonia, hydrogen peroxide, carbon dioxide, metalloids, nitric oxide, and even ions were reported to permeate specific aquaporin, although the mechanism of permeation is still not understood. PROPERTIES OF AQUAPORIN Selectivity of aquaporin

11. Aquaporin are composed of different amino acids that lined the structure of integral protein. One of such amino acids is arginine. This arginine bears a strong positive charge, thus serving to repel protonated water (H 3 O + )/ protons. How do aquaporin eliminate the passage of protons?

12. Maintaining proton gradients across cellular membranes is essential for the bioenergetics of any living cell, as the resulting proton motive force drives numerous transport processes, membrane fusion, and ATP synthesis. Synthesis of ATP is driven by the electro-chemical trans membrane potential associated with the proton gradient, either across the inner mitochondrial membrane in eukaryotes, the thylakoid membrane of chloroplasts in plants, or across the cell membrane in bacteria. Accordingly, leakage of protons across biological membranes would therefore be fatal to the cell. ADVANTAGE OF SELECTIVITY

13. OTHER IMPORTANT FEATURES OF AQUAPORIN GATING OF AQUAPORIN As the movement of water molecules is bidirectional, so the water molecules can also travel from inside of the cell to outside environment depending upon the osmotic gradient. The gating of aquaporin is necessary to keep cells hydrated during periods of drought. The mechanism in some aquaporin involves the de-phosphorylation of certain serine residues, causing the protein to change shape. This change in shape causes the tunnel of the protein to close and not allow any water to pass through. 

14. TRANSPORT OF GLYCEROL Aqua- glyceroporin are involved in skin hydration, cell proliferation, carcinogenesis and fat metabolism. Glycerol permeability in membranes from various tissues and organs has a key role in the regulation of metabolic and energy homeostasis, with the adipose tissue having a pivotal role. Cont …

15. Aquaporin channels are present in different cells of mammals. One of this A quaporin channel is present in kidney. In kidney the reabsorption of water in collecting duct is done by A quaporin channels. It absorb more or less of water according to the need. So, how this aquaporin channel regulate that at this time they have to absorb more or less water it regulated by ADH(anti-diuretic hormone) ADH also called vasopressin . It is hormone secreted by hypothalamus in the brain and stored in the posterior pituitary gland. It tells your kidney how much water to conserve. ADH constantly regulates and balances the amount of water in your blood. AQUAPORIN IN MAMMALS

16. Aquaporin channel in mammals