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Components of Cells
The Macromolecules
Membrane Proteins

Membrane proteins

All living cells are surrounded by a thin, complicated, flexible, waterproof, sensitive, and selfrepairing container that holds the cell together, allows it to grow, feeds it information and stops the contents from escaping. This is the cell membrane.

Although the major component of the membrane, and that which gives it many of its properties, is a double layer of phospholipid molecules, the lipid bilayer, almost all the highly specific functions and properties of membranes are the result of actions and properties of proteins.

The quantity of protein in the average cell membrane varies considerably. Highly specialized membranes, such as those found surrounding a mitochondrion, are more than 70% protein, whereas a human nerve cell in the arm or brain, has only slightly more than 20% protein in its structure.

Hydrophobic and Hydrophilic

The interior and the exterior of cells is liquid, usually a solution or suspension of ions, small molecules and large molecules dissolved in water. Proteins must therefore be hydrophilic ("water loving") in order to be suspended in this environment.

The bilayer of molecules that surround cells, however, is mostly made up of phospholipids arranged in such a way that their hydrocarbon "tails" are all pointing into the center of the structure.

Hydrocarbon molecules are strongly hydrophobic ("water fearing"), and it is this strongly hydrophobic layer of material that gives the cell membrane its "water proof" nature and allows it to act as a container for the cell and its contents. It would be useless to make a container of something that easily dissolved in water!

Proteins associated with a cell membrane, therefore, must be able to interact with both an aqueous, hydrophilic environment, and with the lipid, hydrophobic environment of the inner parts of the membrane.

Crossing the membrane

Some proteins associated with the cell membrane simply connect with one surface or other of the lipid bilayer. They may be attached by way of carbohydrate links, or be complexed with other proteins already embedded in the hydrophobic container.

However, many other proteins extend their structures completely though the bilayer, crossing from one side to another. These transmembrane proteins have regions that easily associate with water (i.e. hydrophilic) and other regions which associate easily with the hydrocarbon dominated center of the bilayer (i.e. hydrophobic).

Other proteins have regions that are hydrophilic, which have no problems in the aqueous environment outside the cell, but also are linked to chains of carbohydrate (oligosaccharides) and then to a separate phospholipid, which has no difficulty fitting into the membrane.

These proteins, called peripheral membrane proteins, are only associated with one side of the membrane or the other - never both.

Only the transmembrane proteins can operate on both sides of the membrane at once, and they often serve to "signal" events taking place outside the cell, to vital functions inside the cell. They also serve as exits and entrances, transporting vital materials from one side of the membrane to the other.

Those regions of the protein that must interact with the strongly hydrophobic center of the lipid bilayer have sequences of polypeptide that are made up of amino acids with hydrophobic R-groups, such as alanine, leucine, glycine, serine and tyrosine.

It is thought that these hydrophobic lengths of polypeptide coil up into a alpha-helical shape.

Red Blood Cell Ghosts

Normal eukaryotic cells contain lots and lots of different proteins, making a study of just those proteins associated with the membranes quite difficult. This problem can be solved, however, if the plasma membranes of human red blood cells are used as a starting material.

Such cells are available in very large numbers, they only have one membrane as part of their structure (the plasma membrane), and it is easy to prepare "ghosts" of these cells by bursting them open in very dilute salt solution and setting free their only contents - the protein hemoglobin.

The remaining, almost pure plasma membrane, can then be studied directly without the problems of contaminating cytoplasmic proteins. Very often the sheets of pure membrane are resealed into tiny globules; tiny "cells" which can be studied for their membrane properties.

The study of plasma membrane proteins prepared in this way has shown that there are about 15 major proteins in or on the membrane, with three of them spectrin, glycophorin, and band-III accounting for about 60% of the total.

Spectrin is found on the inner, cytoplasmic, side of the cell membrane. It is a long, fibrous molecule that makes up about 30% of the total protein found there. It consists of two very large polypeptide chains that wind themselves into a complex that stretches between other protein molecules, such as actin, and several other proteins, including the band-III type and ankyrin.

Together, these proteins appear to form a mesh or network on the inner surface of the red blood cell, which may in turn be responsible for holding the cell in its typical biconcave shape, even as it squeezes through some very, very narrow capillaries in the blood stream.

Glycophorin is a protein that extends all the way through the membrane (it is a transmembrane protein). It consists of 131 amino acids, most of which are found exposed on the outside, external side of the cell. There is also some carbohydrate (about 100 sugar molecules joined into about 16 chains) on the outside. Despite the fact that there can be as many as 6 x 105 of these molecules in the membrane of a typical red blood cell, its function remains a mystery. In fact, red blood cells that lack glycophorin seem to function normally!

band-III protein is also a transmembrane molecule, parts of which cross and re-cross the membrane about three times. It appears that this protein plays an important part in moving carbon dioxide, (carried as the HCO3- ion), through the cell membrane. Since these bicarbonate ions are negatively charged, and thus strongly hydrophilic, they would normally have difficulties getting through the strongly hydrophobic inner part of the membrane.

Parts of the band-III protein passes through the membrane several times, forming a channel through which the anions can pass with a lot less difficulty. This makes it possible for the red blood cells to pick up excess carbon dioxide (produced in the body tissues) and transport them to the lungs for release to the outside.

© 2003, Professor John Blamire