Protein Function

Ligands attach to proteins at specific binding sites on the protein surface. These sites let proteins interact with other molecules or ions and help them carry out important cell functions. Although many possible ligands may be nearby, only a matching ligand can bind to a given protein.

A ligand-binding site has a shape and chemical pattern that fit its ligand. This fit comes from the protein’s amino acid chain, which gives the site its structure and reactivity. The ligand stays in place...

Proteins connect with other proteins to form complexes that carry out cell functions. These protein-protein interactions, or PPIs, are important for an organism's survival. Most PPIs are held together by many weak, noncovalent chemical forces rather than one strong bond.

The shape of the interaction surface helps determine how two proteins fit together. Many globular proteins have surface shapes that match closely and can form many weak bonds. Other PPIs happen between two helices or between a...

Protein ligand-binding pockets help explain how proteins work. A ligand is a small molecule that binds to a specific spot on a protein. These sites are often conserved in related proteins because they are important for function.

When the exact site on a protein surface is not known, it can be predicted. One approach is the energetic method. It examines how amino acid residues interact with the ligand and looks for positions where the binding energy is lowest. Those low-energy regions are...

Protein-ligand binding strength can be measured with the equilibrium binding constant, Kb. This value describes how strongly a protein binds a ligand when the reaction has reached equilibrium. In a bound complex, the protein and ligand are joined as PL, while P and L are the unbound forms.

Kb can be determined in two main ways. One approach uses equilibrium concentrations. The other uses reaction kinetics, which are the rates of binding and unbinding. Kb can also be related to the binding rate...

Cofactors and coenzymes help enzymes work. Many enzymes need these helper molecules to carry out chemical reactions. Without them, the enzyme may not function properly.

A cofactor is a helper molecule that can be either an inorganic ion or an organic molecule. Coenzymes are organic cofactors. They often move between enzymes and help transfer chemical groups or electrons during a reaction.

Some cofactors are vitamins or come from vitamins. These molecules are important because they support...

Allosteric control changes how enzymes work by using a site other than the active site. A small molecule binds to this separate allosteric site and changes the enzyme’s shape. That shape change can alter how well the enzyme binds its substrate and how fast the reaction runs.

Many enzymes use this kind of regulation to turn activity up or down when the cell needs it. In some cases, the allosteric molecule acts as an activator and improves enzyme function. In other cases, it acts as an inhibitor...

Allosteric proteins have more than one ligand binding site. A ligand is a molecule that binds to a protein. When a ligand binds at one site, it can affect binding at the other sites. These sites are called coupled or linked because they influence one another.

In enzymes, the site that binds the substrate is the active site. The other site is the regulatory site. When a ligand binds to the regulatory site, it can change the protein’s shape. This conformational change can then alter how the...

Allosteric switching in multimeric proteins helps explain how ligand binding at one site can change the behavior of the whole protein. In these proteins, each subunit has its own ligand-binding site. When a ligand binds to one subunit, it can cause a shape change that affects the other subunits and their binding sites.

This change in shape comes from the protein’s structure, which includes both flexible and stable segments. A molecule that causes the shift is called a modulator. Because the...

Phosphorylation is a key step in cell signaling. It changes how a molecule behaves by adding a phosphate group. In many cells, this modification helps control activity, shape, and interactions with other molecules.

Phosphorylation is carried out by enzymes called kinases. These enzymes transfer a phosphate group to a target molecule. A phosphatase can remove that phosphate group and reverse the change. Together, kinases and phosphatases help cells turn signals on and off in a controlled way.

Protein control often depends on chemical changes that alter a protein’s charge, shape, and conformation. These changes can include phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis. In cells, these modifications are usually driven by enzymes.

Phosphorylation is one of the most important protein modifications. It adds a phosphate group to a protein and often changes how that protein works. A family of enzymes called kinases...

GTPases are cell proteins that act as signaling switches. They help control cell signaling, vesicle transport, cell shape, and cell movement. When these proteins change or stop working properly, disease can result.

There are about 40,000 known G-proteins. They are usually grouped into two main types. Small G-proteins have one domain, while large G-proteins have multiple domains.

Large G-proteins are also called heterotrimeric G-proteins. They have three subunits: alpha, beta, and gamma. The...

Proteins can be changed after they are made by adding small chemical tags or small proteins. These post-translational modifications help control protein function and stability when the cell environment changes. Common covalent regulators include methyl, acetyl, and phosphate groups, as well as small proteins such as ubiquitin.

About 200 types of covalent regulators have been identified. These tags attach to specific amino acids in a protein. Phosphate groups can attach only to serine,...

The SCF ubiquitin ligase is a protein complex that uses an F-box protein to help choose which target proteins get marked for destruction. This complex is made of five separate proteins, and each one has a different job. Together, they attach ubiquitin to target proteins so the cell can send those proteins to be degraded.

The F-box protein is the part that binds the substrate, or target protein. That binding step lets the ubiquitin-conjugating enzyme reach the target and attach ubiquitin. In...

Proteins can create and respond to mechanical force in cells. Some proteins generate force, while others are pulled or stretched by it. Proteins such as keratin provide structural support and are subjected to mechanical force. Proteins such as ion pumps help move molecules across cell membranes and can generate mechanical force.

Cell movement and muscle contraction depend on turning chemical energy into motion. This often happens through conformational change, which is a shift in a protein’s...

Structural proteins give cells and tissues shape, support, and strength. They help build bones, cartilage, hair, and muscles. Important examples include collagen, actin, myosin, and keratin.

Collagen is the most abundant protein in mammals. It is found throughout the body. In skin, ligaments, and tendons, collagen adds tensile strength and elasticity. In bones and teeth, it helps form hard, load-bearing tissue through mineralization.

Collagen also does more than provide support. It can...

Mapping protein interactions shows how proteins work together in a cell. Many proteins must connect with other proteins to carry out their jobs and keep an organism healthy. These connections can be shown as protein-protein interaction networks, also called protein maps.

In these maps, proteins are shown as nodes, or circles. Lines called edges connect two proteins that interact. The network can include stable interactions, such as those in protein complexes, and transient interactions that...

ATCase is a key enzyme in pyrimidine synthesis. It is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to form N-carbamoyl-L-aspartate. This reaction starts the pathway that makes pyrimidines.

ATCase is regulated by feedback inhibition. The end products UTP and CTP bind to the enzyme and reduce its activity when pyrimidine levels are high compared with purines in the cell. This binding at one site affects the linked catalytic site, which helps keep...