Structural Biochemistry/Enzyme Catalytic Mechanism/Integral Membrane Protein

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An integral membrane protein (IMP) is a protein molecule directly attached to a phospholipid bilayer and serves as a structural and functional part of a cells membrane. Structurally, they traverse the hydrophobic phospholipid bilayer and can only be removed by detergents and denaturants that disrupt the hydrophobic interactions.

Structure[edit | edit source]

Currently, in three dimensional structure of only around 160 integral membrane proteins have been visualized through X-ray crystallography and nuclear magnetic resonance because of the difficulty in isolating the proteins and pure crystal growth. Integral membrane proteins can be categorized into two groups: Integral polytopic proteins (Transmembrane proteins) and integral monotopic proteins.

The portions of the protein located in the hydrophobic center of the bilayer are usually arranged into alpha helices so that the polar amino and carboxy groups can interact with each other rather than with the hydrophobic surroundings. The portion that projects out of the bilayer tends to have a large amount of hydrophilic amino acids.

Integral Polytopic Proteins[edit | edit source]

Transmembrane proteins are the most popular IMP and traverse the entire cell membrane. Single pass membrane proteins cross the membrane just once while multi pass membrane proteins cross the membrane several times. Single pass proteins can either have their carboxy end towards the cytosol or their amino end directed at the cytosol.

Integral Monotopic Proteins[edit | edit source]

Integral monotopic proteins are only attached to one side of the phospolipbilayer. Three dimensional structures have been deduced for

  • prostaglandin H2 syntheses 1 and 2 (cyclooxygenases)
  • lanosterol synthase and squalene-hopene cyclase
  • microsomal prostaglandin E synthase
  • carnitine O-palmitoyltransferase 2

Function[edit | edit source]

Integral membrane proteins function as transporters, channels (see Potassium Channel), linkers, receptors, proteins involved in accumulation energy, and proteins responsible for cell adhesion. Examples include insulin receptors, Integrins, Cadherins, NCAMs, and Selectins.

Integral membrane protein movement and distribution[edit | edit source]

Many proteins are free to move laterally in the plane of the bilayer. One experiment used to show this involved fusing cultured mouse cells with human cells under appropriate conditions to form a hybrid cell known as a heterokaryon. The mouse cells were labeled with mouse protein-specific antibodies to which the green-fluorescing dye fluorescein had been covalently attached, whilst the human cells were labeled with the red-fluorescing dye rhodamine. Upon cell fusion, the mouse and human proteins as seen under the fluorescence microscope were segregated on the two halves of the heterokaryon. After 40 minutes at 37oC, however, the mouse and human protein had completely intermingled. Lowering the temperature to below 15oC inhibited this process, indicating that the proteins are free to diffuse laterally in the membrane and that this movement is slowed as the temperature is lowered. It should be noted, though, that some integral membrane proteins are not free to move laterally in the membrane because they interact with the cytoskeleton inside the cell.

The distribution of proteins in membranes can be revealed by electron microscopy using the freeze-fracture technique. In this technique,a membrane specimen is rapidly frozen to the temperature of liquid nitrogen and then fractured by a sharp blow. The bilayer often splits into monolayers, revealing the interior. The exposed surface is then coated with a film of carbon and shadowed with platinum in order for the surface to be viewed in the electron microscope. The fractured surface of the membrane is revealed to have numerous randomly distributed protuberances that correspond to integral membrane proteins.

Reference[edit | edit source]

Hames, David. Hooper, Nigel. Biochemistry. Third edition. Taylor and Francis Group. New York. 2005.