Aquaporin

Aquaporins ( AQP) are proteins that form the channels in the cell membrane to facilitate the passage of water and some other molecules ( membrane transport). They are therefore also called water channels. Aquaporins come in all living things before with the cell membrane; they were found in archaea, bacteria and eukaryotes.

Since biomembranes in its interior are water repellent (hydrophobic ), its conductance to water molecules is very low. The water conductivity of a Aquaporinkanals is, however, up to 3 billion molecules per second. The protein family of aquaporins is divided into so-called ordinary aquaporins and Aquaglyceroporins. Ordinary aquaporins are pure water channels. Aquaglyceroporins conduct additional small organic molecules such as glycerol or urea. Under physiological conditions occur aquaporins as a tetramer, ie four Aquaporinkanäle are installed as a unit in a biological membrane.

History

The fact that water can be transported across cell membranes, has long been known. The first speculations and discussions on the mechanism rich in the middle of the 19th century ( and Others Ernst Wilhelm Bridge was involved in it ). After the discovery of the double lipid layer in plasma membranes in the late 1920s it started with the simple diffusion of water through the cell membrane, but could not explain the very different permeabilities of different cells. In the 1970s, it was, inter alia, by Arthur Solomon, Robert Macey and Alan Finkelstein posits the existence of specific water channels due to biophysical models. The problem of identification is quite complex: water is available everywhere and it can not be modified by photo- sensitive side chains. Even attempts at genetic cloning of the corresponding proteins did not lead to success.

It was not until the early 1990s, succeeded by the group of Peter Agre, a well-known from earlier studies on Rhesus blood group antigens protein ( CHIP28 ) with hitherto unknown function to be identified as this water channel. They named this protein then aquaporin -1 ( AQP1 ). In 2003 he received the Nobel Prize in Chemistry for his research in the field of aquaporins. To date, a number of aquaporins in humans, in animals, plants and bacteria have been identified.

Structure

All known aquaporins have a similar structure and amino acid sequence. The primary structure of AQP1 consists of 268 amino acids. These form the six α -helices which span across the membrane ( an integral membrane protein). Interconnected helices of the loops ( loops) A to E are playing a special role in the loops B and E, each of which forms a short helix that plunge from both sides to the middle of the membrane. On each of the two loops at the end of the two short helices, is a characteristic structural motif consisting of three amino acids (N -P -A, asparagine -proline- alanine), which contributes significantly to the selectivity of the water channel. Each of the two loops forming a Halbpore, which together form a water channel ( Hour -Glass Model, Sanduhrmodell ). The channel is narrowest at the middle ( 0.3 nm ), at the two openings, the diameter of 2 nm, the carboxy-and amino-terminal ends of the membrane protein located in the cell interior. In biological membranes, aquaporins form homotetramers, which means that anneal four individual functional pore proteins.

Function

Water is able to diffuse to a limited extent through the lipid bilayer of the cell membrane. Cells with very high water permeability, such as the renal tubular cells, secretory cells of the salivary glands or erythrocyte need for the rapid exchange of water the aid of water channels. The difference between diffusion and channel- mediated permeability is significant. Diffusion is a process that occurs with a low capacity in both directions through the membrane of all cells. In the presence of specific water channels, water can almost freely migrate in the direction of the osmotic gradient. The aquaporins are no pumps or exchangers and transport is no metabolic energy consumed. The channel is bidirectional, that is, water can travel in both directions through the channel. While the diffusion through the membranes can not be blocked, aquaporins can by molecules that clog the pores, and thus blocked the flow of water will be interrupted. Some aquaporins can by mercury compounds which bind covalently to a cysteine ​​side chain in the pore are clogged.

Proton blockade

Aquaporins are highly selective. In particular, they prevent the direction of protons across the membrane, so that the proton gradient essential for each cell is not destroyed. ( The proton gradient is used to provide transport processes - see, for example, ATPases ). This is not self-evident, since water is not present in the liquid phase as a single molecule, but as a means of hydrogen bonds interconnecting network. Along these hydrogen bonds proton from molecule to molecule hopping ( Grotthuss mechanism).

As the hopping of protons is prevented by the channel, is the subject of current research. Of significance seems to be that aquaporins due to their structure, an electrostatic barrier in the middle of the channel. This has the consequence that the polar water molecules with their partial negatively charged oxygen are generally oriented toward the center of the channel, while the partially positively -charged hydrogen are usually oriented to the channel outputs. Early work (2002 ) suggested, therefore, that the Grotthuss mechanism is interrupted by the orientation of the water molecules.

Recent work doubt this interpretation and provide the energy barrier that must be overcome, the proton along the channel in the foreground. Subject of current debate (as of July 2007) is the origin of the energy barrier. While some scientists move the electrostatic barrier created by the protein in the foreground, highlight other that the protein can not replace the solvation of a proton / hydronium ion in water.

Inhibition

Aquaporin -1 of mercury, gold or silver ions inhibited ( inhibited ). In this case, the ion binding to a cysteine ​​in the pore entrance, thereby blocking the flow of water. These ions do not specifically bind to aquaporin -1 and are therefore toxic. The search for specific Aquaporininhibitoren is the subject of current research.

Facilitated intracellular water diffusion in plants

The function of aquaporins in plant cells could be characterized as components of the facilitated cellular water diffusion and their occurrence could be detected in plant tissue. A specific protein aquaporin- class results in the facilitated diffusion of CO2 in plant tissue and cells or chloroplasts.

Importance

From physiological importance aquaporins are found mainly in tissues where a high physiological flow occurs, for example, in the construction of Turgordrucks in plant cells.

  • In mammals, aquaporins regulate the water balance of red blood cells (RBCs ) and the cells in the kidney, eye lens, brain, and cochlea of the inner ear.
  • In liver bile ducts and gallbladder aquaporins are responsible for the concentration and secretion of bile.
  • In the central nervous system contain cells which secrete cerebrospinal fluid, water channels. They play an important role in blood -brain barrier and appear there in the form of orthogonal combinations that are called OAP 's (orthogonal arrays of particles ).
  • In the cells of the blood capillaries, they regulate the entry and exit of the extracellular fluid.
  • In the alveoli, they provide the necessary gas exchange liquid film.
  • In plants, chloroplasts and they make for facilitated diffusion.

Malfunction of aquaporins are for diseases such as diabetes insipidus, renal, cataract, glaucoma ( glaucoma) and hearing loss responsibility. In addition, aquaporins play at the occurrence of cerebral edema after a traumatic brain injury a role.

Nomenclature

  • If aquaporins are simply numbered ( AQP1, AQP4 ), this means that it is animal organisms. Normally, nor the corresponding Latin genus name is prefixed, for example bovAQP1 (Latin bos, bovis = cattle).
  • Pflanzenaquaporine be named differently. So does AtTIP2; 1 that there is a tonoplast intrinsic protein of the ( model ) plant thale cress (Arabidopsis thaliana ).

Variants

CHIPs (English channel- forming integral proteins) are located in the cell membrane of red blood cells and kidney cells. In mammals, the density of aquaporins is particularly high in erythrocytes ( approximately 200,000 channels per cell ) and in the proximal tubule cells of the kidney, which reabsorb the water in the formation of urine.

AQP2, which is found in cells of the collecting ducts of the kidney (hence the old name of WCHDs engl. Colleng water channels of Conduct ) is stored in vesicles. If no water is the hormone vasopressin is secreted by the pituitary gland. Vasopressin binds to specific membrane receptors AQP2 -containing cells and is a signaling cascade in motion. This causes the vesicles to fuse with the cell membrane, making the absorption of water from the primary urine is increased by a factor of twenty.

TIPs (English tonoplast intrinsic proteins ) are integrated in plants in the membrane of the vacuole during cell growth and provide for the increase in volume of the cell due to water absorption.

PIPs ( plasma membrane intrinsic proteins engl. ) are also to be found only in plants and regulate the water line by the cells. In this manner, in addition to the xylem Wasserleitgefäßen a second water transport system with the other plant tissue.

Nobel prize

Roderick MacKinnon (Rockefeller University, New York ) and Peter Agre ( Johns Hopkins University, Baltimore ) received the 2003 Nobel Prize in Chemistry for her research on aquaporins and potassium channels.

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