Carrier proteins are important transmembrane polypeptide molecules which facilitate the movement of charged and polar molecules and ions across the lipid bilayer structure. The transported solutes may be small organic molecules or inorganic ions and are often highly selective. A variety of carrier proteins are also seen on the inner membranes of organalle of the cell.
Carrier proteins typically have a binding site which will only bind to the substance they’re supposed to carry. Once the carrier protein has bound to a sufficient quantity of its target substance, the protein changes shape to carry the substance from one side of the membrane to the other. Some carrier proteins require no energy sources but the diffusion gradient that their substrate wants to pass down, making them a form of passive transport. Others may require energy in the form of ATP, or may perform secondary active transport, where the transport of one substance against its diffusion gradient is powered by a different diffusion gradient that is created by ATP-using carrier proteins.
Based on the transport mechanism as well as genetic and structural homology, there are considered four classes of ATP-dependent ion pumps:
- P-class pumps:
The functional mechanism of these pumps is the phosphorylation of the α (alpha) subunit of the protein by the ATP, which will induce a change in its conformation and making transport possible. Examples are Na+/ K+-ATPase, Ca2+-ATPase, H+/ K+-ATPase .
- F-class pumps:
It only pumps H+ (proton) and its activity does not involve a phosphoprotein as an intermediate. It has an important role in ATP synthesis, and so can also be called ATP synthase. This pump usually runs in the opposite direction, generating ATP by using the protonmotive force created by the electron transport chain as a source of energy. The general process of creating energy in this way is called oxidative phosphorylation. This process takes place in the mitochondria, where ATP synthase is located in the inner mitochondrial membrane.
- V-class pumps:
V-class pumps pumps exclusively protons. It is present in animal lysosomal and endosomal membranes. Unlike P-class ion pumps, the V-class H+-ATPases are not phosphorylated and dephosphorylated during proton transport, thus a phosphorylated protein is not an intermediate in transport. It is responsible for maintaining a lower pH inside the organelles than in the surrounding cytosol, which is important for the activity of the lysosomal and endosomal enzymes.
- ABC superfamily:
It is also known as ATP-binding cassette. Each ABC protein is specific for a single substrate or group of related substrates. All ABC transport proteins contain 4 core domains: 2 transmembrane (T) domains, which form a pathway for solute movement and determine substrate specificity and 2 cytosolic ATP-binding (A) domains It includes more than 100 different transport proteins found in organisms ranging from bacteria to humans.
The P-, F- and V-classes only transport ions, while the ABC superfamily also transports small molecules.
Examples of Carrier Proteins
- Sodium-Potassium Pump (Na+/K+ ATPase)
The cytosol of animal cells contains a concentration of potassium ions (K+) as much as 20 times higher than that in the extracellular fluid. Conversely, the extracellular fluid contains a concentration of sodium ions (Na+) as much as 10 times greater than that within the cell.
These concentration gradients are established by the active transport of both ions. And, in fact, the same transporter, called the Na+/K+ ATPase, does both jobs. It uses the energy from the hydrolysis of ATP to actively transport 3 Na+ ions out of the cell for each 2 K+ ions pumped into the cell.
This accomplishes several vital functions:
- It helps establish a net charge across the plasma membrane with the interior of the cell being negatively charged with respect to the exterior. This resting potential prepares nerve and muscle cells for the propagation of action potentials leading to nerve impulses and muscle contraction.
- The accumulation of sodium ions outside of the cell draws water out of the cell and thus enables it to maintain osmotic balance (otherwise it would swell and burst from the inward diffusion of water).
- The gradient of sodium ions is harnessed to provide the energy to run several types of indirect pumps.
The crucial roles of the Na+/K+ ATPase are reflected in the fact that almost one-third of all the energy generated by the mitochondria in animal cells is used just to run this pump.
- Calcium pump (Ca2+ ATPases)
A Ca2+ ATPase is located in the plasma membrane of all eukaryotic cells. It uses the energy provided by one molecule of ATP to pump one Ca2+ ion out of the cell. The activity of these pumps helps to maintain the ~20,000-fold concentration gradient of Ca2+ between the cytosol (~ 100 nM) and the extracellular fluid (~ 20 mM).
In resting skeletal muscle, there is a much higher concentration of calcium ions (Ca2+) in the sarcoplasmic reticulum than in the cytosol. Activation of the muscle fiber allows some of this Ca2+ to pass by facilitated diffusion into the cytosol where it triggers contraction.
After contraction, this Ca2+ is pumped back into the sarcoplasmic reticulum. This is done by another Ca2+ ATPase that uses the energy from each molecule of ATP to pump 2 Ca2+ ions.
- Hydrogen potassium pump (H+/K+ ATPase)
H+/K+ ATPase is the proton pump of the stomach. It exchanges potassium from the intestinal lumen with cytoplasmic hydronium and is the enzyme primarily responsible for the acidification of the stomach contents and the activation of the digestive enzyme pepsin.
The parietal cells of your stomach use this pump to secrete gastric juice. These cells transport protons (H+) from a concentration of about 4 x 10-8 M within the cell to a concentration of about 0.15 M in the gastric juice (giving it a pH close to 1). Small wonder that parietal cells are stuffed with mitochondria and uses huge amounts of ATP as they carry out this three-million fold concentration of protons.
- ATP-Binding Cassette (ABC) transporters
ABC transporters are transmembrane proteins that expose a ligand binding domain at one surface (transmembrane domain – TMD) and a ATP-binding domain (nucleotide-binding domain -NBD) at the other surface. The ligand-binding domain otherwise called membrane-spanning domain (MSD) or integral membrane (IM) domain is usually restricted to a single type of molecule and undergoes conformational changes to transport the substrate across the membrane. The ATP bound to its domain provides the energy to pump the ligand across the membrane.
The sequence and architecture of TMDs is variable, reflecting the chemical diversity of substrates that can be translocated. The NBD or ATP-binding cassette (ABC) domain, on the other hand, is located in the cytoplasm and has a highly conserved sequence.
ABC transporters are the members of a transport system superfamily that is one of the largest and is possibly one of the oldest families. The human genome contains 48 genes for ABC transporters and the mutations in human genes can cause or contribute to several human genetic diseases.
Some examples of ABC transporters are:
- CFTR — the cystic fibrosis transmembrane conductance regulator
- TAP, the transporter associated with antigen processing.
- The transporter that liver cells use to pump the salts of bile acids out into the bile.
- ABC transporters that pump chemotherapeutic drugs out of cancer cells thus reducing their effectiveness.
- Sodium-Glucose (Na+/glucose) cotransporter
Na+/glucose transporters are a family of glucose transporter found in the intestinal mucosa (enterocytes) of the small intestine (SGLT1) and the proximal tubule of the nephron (SGLT2 in PCT and SGLT1 in PST). They play an important role in renal glucose reabsorption.
The sodium-glucose co-transport protein is a good example of a protein that uses secondary active transport, by indirectly using ATP. Firstly, an Na+/K+ ATPase pump on the basolateral membrane of the proximal tubule cell uses ATP molecules to move 3 sodium ions outward into the blood, while bringing in 2 potassium ions. This action creates a downhill sodium ion gradient from the outside to the inside of the proximal tubule cell (that is, in comparison to both the blood and the tubule itself). The SGLT proteins use the energy from this downhill sodium ion gradient created by the ATPase pump to transport glucose across the apical membrane, against an uphill glucose gradient. It is an example of symport transport as the driving ion (Na+) and the pumped glucose molecule pass through the membrane pump in the same direction.