16.8: Membrane Proteins

The positions of the proteins within the membrane lead to their classification as integral proteins and peripheral proteins (Figure 1). Integral proteins commonly feature domains of alpha-helical segments that span the membrane and assume many roles⁶. One such example is channel proteins, which exert selective control over the passage of materials into or out of the cell (Figure 4). Integral proteins also play a crucial role in cellular function by serving as pores, specific openings within the cell membrane that facilitate the controlled movement of substances in and out of the cell. Furthermore, integral proteins act as ion pumps. Their selective permeability and controlled gating mechanisms ensure that the cell maintains an appropriate internal environment while allowing for the exchange of essential molecules with the outside. Integral proteins also serve as cell recognition markers and receptors. Some integral proteins undertake a dual role, acting as both receptors and ion channels. Additionally, integral proteins may serve as enzymes. In contrast, peripheral proteins occupy positions on the inner or outer lipid bilayer surface. These proteins typically fulfill specialized functions, including participation in intracellular signaling and contribution to the submembranous cytoskeleton. An exemplary scenario entails the peripheral proteins on the surface of intestinal epithelial cells, which act as digestive enzymes.

Figure 4 | A Phospholipid Bilayer along with Membrane Proteins | ⁷ Integral proteins span the lipid bilayer and may serve as pores or ion channels. Peripheral proteins occupy positions on the inner or outer lipid bilayer surface.

Due to the closely packed arrangement of phospholipid molecules in the membrane, only small nonpolar molecules like oxygen and carbon dioxide can swiftly traverse it. Transport of charged particles, such as ions, occurs via specific membrane proteins functioning as channels. Water, a small polar molecule, moves through membrane pores. Large polar molecules, such as glucose, necessitate specific transport mechanisms and cannot permeate the cell membrane.

Carbohydrates associated with integral proteins extend into the extracellular matrix, aiding in cell recognition. Together with those linked to membrane proteins and phospholipids, these carbohydrates create the glycocalyx⁸, a thin coating that envelops the cell, enabling it to bind to other cells and carry receptors or enzymes.

Channels

Channel proteins can be differentiated into open and closed types based on whether their conformation creates a passage for ions or molecules (open) or obstructs it (closed) in response to specific triggers. Their functionality and responses to stimuli play a crucial role in cellular processes such as signaling, neurotransmission, and maintaining ion gradients ⁹. Channel proteins with open pores are in a conformation that allows them to create a pathway through the cell membrane that permits the passage of ions or molecules where the movement typically occurs down their concentration gradient. Closed channel proteins may transition to an open state in response to specific triggers, such as voltage changes, ligand binding, or mechanical stimuli. A leakage channel, on the other hand, exhibits a random pattern of opening and closing, lacking any specific triggering event as it switches between its open and closed states at an intrinsic rate.

Ion Channels

As the name suggests, ion channels are membrane channel proteins that facilitate the passage of specific ions. The channel's pore is tailored to the charge it accommodates. Proteins spanning the cell membrane, including its hydrophobic core, can interact with ion charges. The ions interact with hydrophilic amino acids based on the ion's charge. Channels designed for cations possess negatively charged side chains in their pores, whereas those for anions have positively charged side chains. Pore diameter differs among various channel types. Larger pore sizes are less favorable for smaller ions due to enhanced interaction between water molecules and amino acid side chains. Certain ion channels are charge-selective rather than size-selective, making them nonspecific channels. These nonspecific channels permit cations, including sodium, potassium, and calcium ions, to traverse the membrane while excluding anions.

Ligand-gated Channels

Ligand-gated channels are specialized membrane protein channels that respond to the binding of specific signaling molecules, known as ligands. These channels play a critical role in cell communication and the transmission of signals across the cell membrane. When a ligand, such as a neurotransmitter, hormone, or other signaling molecule, binds to the receptor site on the ligand-gated channel, the channel undergoes a conformational change. This change in shape leads to the opening of the channel, allowing the passage of ions or other molecules across the membrane (Figure 5). It is crucial for various physiological processes, including nerve impulse transmission, muscle contraction, and cell-to-cell communication. Ligand-gated channels provide a rapid and specific response to extracellular signals, allowing cells to communicate with each other and coordinate various physiological activities efficiently. The binding of the ligand is reversible, meaning that once the ligand dissociates from the receptor site, the channel undergoes another conformational change, leading to channel closure.

Figure 5| Ligand-gated Channels | ¹⁰ When the ligand, such as the neurotransmitter acetylcholine (ACh), attaches to a designated site on the outer surface of the channel protein, it triggers the opening of the pore, facilitating the passage of specific ions. In this scenario, the ions include sodium (\(\ce{Na+}\)), calcium (\(\ce{Ca++}\)), and potassium (\(\ce{K+}\)).

Mechanically-gated Channels

When a protein channel reacts to physical changes in the membrane, such as pressure or touch, it is known as a mechanically-gated channel. These channels permit ion entry when an external force is applied, such as when pressure is exerted on the skin (Figure 6). Thermoreceptors are equipped with mechanically-gated channels that respond to alterations in tissue temperature by opening their ion channels.

Figure 6 | Mechanically-gated Channels | ¹¹ When a mechanical change occurs in the surrounding tissue, such as pressure or touch, the channel is opened. Calcium ion (\(\ce{Ca++}\)); Sodium ion (\(\ce{Na+}\))

Voltage-gated Channels

A voltage-gated channel responds to alterations in the membrane's electrical characteristics at its location. For instance, specific voltage-gated channels might open in a cell with a membrane potential of -70 mV if the voltage becomes less negative, thus allowing ions to flow into the cell (Figure 7).

Figure 7 | Voltage-gated Channels | ¹² In this illustration, a voltage-gated channel remains closed at a membrane voltage of -70 mV (Left) and opens when the transmembrane voltage reaches -50 mV (Right).

Leakage Channels

A leakage channel is the simplest type of channel, opening and closing randomly without any specific trigger, and operates at an inherent rate. Leakage channels are linked to the resting membrane potential (Figure 8).

Figure 8 | Leakage Channel | ​¹³ Opening and closing of the leakage channel occurs randomly allowing passage of ions when it is open.