Structure and Function of Transmembrane Proteins

Cell membrane proteins are usually covered with carbohydrates, like oligosaccharides (to form glycoproteins) or polysaccharides (to form proteoglycans), before they protrude out of the cell membrane.

Biological membranes are usually made of lipid bilayers and proteins. The proteins that comprise these membranes are usually known as membrane proteins. These proteins can either be classified as integral or intrinsic proteins and extrinsic or peripheral proteins.

Peripheral proteins do not remain attached to the membrane permanently or attach to integral proteins by non-covalent interactions. Integral proteins, on the other hand, are permanently attached to the cell membrane.

Some integral proteins attach to only one side of the membrane, and do not span across it; these proteins are known as integral monotopic proteins. Another class of integral proteins are integral polytopic or transmembrane proteins that tend to span across the cell membrane.

Transmembrane proteins span entirely or from one side of the cell membrane through to the other. These proteins basically function as gates or docking sites that allow or prevent the entry or exit of materials across the cell membrane.

These proteins are usually classified either on the basis of the topology of their structure.

The topology of a transmembrane protein basically describes the number of the membrane-spanning domains. If the protein has only one transmembrane domain, we call it a single-pass transmembrane protein; when the protein has two or more membrane-spanning domains, it is known as multi-pass transmembrane domain.

It also refers to the location (whether on the cytosolic side or the non cytosolic side) of the N-terminus of the protein on the biological membrane.

Type I: It is a single-pass transmembrane protein which has its N-terminal domain targeted outside the cell.

Type II:The N terminus of the protein is close to the transmembrane domain of the protein and functions as an anchor. Here the N terminus is targeted towards the cytosol.

Type III:The N-terminus of the protein is targeted outside the cell. It forms the transmembrane domain of the protein and is used to anchor the protein to the cell.

Type IV:Here, the N-terminal domain is located inside the cell. The protein is anchored to the cell membrane with the help of its C-terminal domain.

Type 1:These proteins are attached to the lipid membrane with the help of covalent bonds.

Type 2:These proteins have a transmembrane domain as well as lipid anchors that are attached to the cell membrane via covalent bonds.

Transmembrane protein can either be classified as α helical structures or as β strands. Let us understand the structure of α helical transmembrane proteins with the help of an example.

Glycophorin is a major transmembrane protein present in the erythrocyte cell membrane. It is a single-pass transmembrane protein. These proteins exhibit both hydrophobic and ionic interactions with the cell membrane.

This protein is seen to possess hydrophobic or uncharged amino acids that form the α helical structure that is embedded in the cell membrane. These hydrophobic amino acids form Van der Waals interactions with the fatty acid chains of the cell membrane.

These interactions shield the charged carbonyl carbon and the imine groups of the peptide bond (that already form H bonds with each other). These hydrophobic amino acid sequences are flanked by the positively amino acids, lysine and arginine. These positively charged amino acids interact with the negatively charged polar heads of the phospholipid bilayer.

This prevents the slipping of the hydrophobic α helical structure off the cell membrane. In glycophorins and other α helical structures, the transmembrane domain is usually hydrophobic, whereas the cytosolic extension of these proteins are usually polar.

It is a biological pigment present in the rod cells of the retina, which plays a role in the visual phototransduction pathway. This protein is also covalently bound to retinal. It contains seven membrane-spanning helical structures. The membrane-spanning domains are hydrophobic, whereas the loops connecting the adjacent transmembrane domains are hydrophilic in nature.

There are many opsins that have very similar structures, one such example is the bacteriorhodopsin. Just like other opsin, it too has seven transmembrane domains with the N-terminus domain targeted outside the cell, and the C-terminus domain targeted in the cytosolic region.

Several transmembrane proteins contain multiple β strands that can be described as "membrane forming barrels". We will discuss the basic structure of these β barrels with the help of porin molecules. Porins are present in the cell membrane of a number of gram negative bacteria like E. Coli.

They selectively allow the passage of nutrients and waste products, whereas they prevent the uptake of harmful substances like antibiotic and bile salts.

Porins are mostly made of hydrophilic amino acid sequences and contain few hydrophobic residues. X-ray crystallographic studies have revealed porins to be trimers of identical subunits.

Each subunit is composed of hydrophobic amino acids on the outer side that interacts the hydrophobic cell membrane or other subunit. The inner side of porin is lined with hydrophilic amino acids that facilitates the passage of small water-soluble molecule across the cell membrane.