5.9: Introduction to Membrane Proteins

The cell membrane, or plasma membrane, is an ever-changing landscape. It is described as a fluid mosaic where various macromolecules are embedded in the phospholipid bilayer. Among the macromolecules are proteins. The protein content varies across cell types. For example, mitochondrial inner membranes contain ~76% protein content, while myelin contains ~18% protein content. Individual cells contain many types of membrane proteins—red blood cells contain over 50—and different cell types have distinct membrane protein sets.

Membrane proteins have wide-ranging functions. For example, they can be channels or carriers that transport substances, enzymes with metabolic roles, or receptors that bind to chemical messengers. Like membrane lipids, most membrane proteins contain hydrophilic (water-attractive) and hydrophobic (water-repelling) regions. The hydrophilic areas are exposed to water-containing regions inside the cell, outside the cell, or both. The hydrophobic regions face the hydrophobic tails of phospholipids within the membrane bilayer.

Membrane proteins can be classified by whether they are embedded (integral) or associated with the cell membrane (peripheral). Most integral proteins are transmembrane proteins, which traverse both phospholipid layers and span the entire membrane. Their hydrophilic regions extend from both sides of the membrane, facing the cytosol on one side and the extracellular fluid on the other. In contrast, the hydrophobic regions consist of coiled amino acid groups (α-helices or β-barrels). Integral monotopic proteins are attached to only one side of the membrane.

Peripheral proteins are not embedded in the phospholipid bilayer and do not extend into its hydrophobic core. Instead, they temporarily adhere to the outer or inner surfaces of the membrane, attached to integral proteins or phospholipids. Membrane proteins that extend from a cell's external surface often carry carbohydrate chains, forming glycoproteins. Some glycoproteins facilitate cell-to-cell recognition by functioning as "ID tags" that can be recognized by membrane proteins of other cells.

Membrane proteins fall into two major categories— peripheral and integral.

Peripheral proteins associate with phospholipid heads or hydrophilic domains of integral proteins by non-covalent interactions.

Many peripheral proteins participate in cell signaling cascades as they can easily detach from the membrane. Other peripheral proteins link the membrane with the cytoskeleton, providing structural support.

Integral proteins are amphipathic molecules with their hydrophilic regions facing the cytoplasm or extracellular fluid and the hydrophobic domain embedded within the phospholipid tails. 

Transmembrane proteins are a type of integral protein that span the entire plasma membrane. They often play important roles in the cell, including serving as transporters, enzymes, and receptors.

The membrane-spanning parts of these proteins can be a single alpha helix, multiple alpha helices, or a larger beta barrel that has a pore through the center.

Lipid-anchored proteins have attached lipid chains that fasten them to the membrane.