Proteins

Protein Structure and Function

Levels of Protein Structure

Proteins are composed of amino acids folded in complex configurations called groups, and large protein molecules may contain multiple polypeptide chains.
Of the four types of organic molecules that make up a cell, proteins are the most abundant and functional of organic substances. Deoxyribonucleic acid, or DNA, contains the instructions for the genetic makeup of organisms, and proteins serve as the mechanisms by which cells function. Proteins play roles in cell structure, communications, defense, transport, metabolism, and movement. All proteins in the human body are unbranched chains of some combination of the same 20 building blocks, called amino acids; an amino acid is an organic molecule that contains a carboxyl group (COOH{-}{\rm{COOH}}), an amino group (NH2{-}{\rm{NH}}_2), and a functional side chain, which is a group of atoms unique in its structure and function.

Amino Acids

Essential Conditionally Essential Non-Essential
Histidine Arginine Alanine
Isoleucine Asparagine Aspartate
Leucine Glutamine Cysteine
Methionine Glycine Glutamate
Phenylalanine Proline
Threonine Serine
Tryptophan Tyrosine
Valine
Lysine

Of the 20 amino acids, nine are considered essential because the human body cannot synthesize them. These must be obtained from food. Seven amino acids are "conditionally essential," meaning they cannot be made in some situations but can be made in others. The remaining four amino acids are made in the human body and do not have to be obtained from food.

Amino acids consist of a central carbon atom, known as the alpha carbon, with four covalent bonds, or chemical bonds that are made by sharing electrons between atoms. One bond is made to a carboxyl group, which is a portion of a molecule made of a carbon atom bonded to one oxygen atom and one hydroxyl group, written (COOH{-}{\rm{COOH}} ). Another is made to an amino group, which is a portion of an amino acid made up of a nitrogen atom bonded to two hydrogen atoms (NH2{-}{\rm{NH}}_2). A third bond is made to a hydrogen atom, and a fourth to an R group, alternatively called a side chain, which is one of the 20 possible groups that give amino acids their distinct chemical identities. R groups may be water loving, or hydrophilic—seeking to bond with aqueous solutions—and be polar amino acids, such as cysteine or serine. They may be nonpolar, such as alanine or glycine, and avoid contact with aqueous solutions. Each group has a specific structure and function, and the interactions of these amino acids provide the three-dimensional structures of proteins. Each of the 20 amino acids has a different R group. These chemically diverse groups provide information for identifying the different amino acids.

Chemical Structure of an Amino Acid

The chemical structure of an amino acid includes an amino group and a carboxyl group, which react to form the peptide bonds of the protein backbone, and an R group that gives the amino acid its distinct chemical identity.
When the carboxyl group of one amino acid bonds via a dehydration synthesis reaction with the amino group of another amino acid, a peptide bond is formed, which is a named covalent bond. A dehydration synthesis reaction is the mechanism through which two molecules join once water is removed. Amino acids joined in this way form a polypeptide chain. A series of peptide bonds is the backbone of every protein. The primary structure of a protein is the sequence of amino acids it contains. All the bonds involved in the formation of the primary structure are covalent (peptide) bonds.

In contrast, proteins' secondary structure, or two stable folding patterns known as alpha helices and beta sheets, is the result of hydrogen bonding that occurs between relatively closely positioned amino acids on the same polypeptide chain. An alpha helix, or α\alpha-helix, is a right-handed, spiraled polypeptide chain, while a beta sheet, or β\beta-sheet, is shaped like an accordion. Hydrogen bonding is an attraction between a partially positively charged hydrogen atom and another atom with a partial negative charge. The hydrogen bonds that form alpha helices and beta sheets occur between the carboxyl groups and amino groups of the protein backbone, so these patterns occur in most proteins, such as the bond that occurs with the enzyme lysozyme. Alpha helices are formed when the hydrogens and oxygens of amino acids relatively close to one another interact with each other. Beta sheets form from the interactions that occur between local amino acid strands, called interstrand interactions. Specifically, the carbonyl oxygen atoms of one strand form hydrogen bonds with amino hydrogen atoms of an adjacent strand. The strands lying side by side form the sheet conformation. The strands may run parallel or antiparallel to one another, forming one of two types of beta sheet, parallel beta sheet or antiparallel beta sheet, respectively. Parallel beta sheets have peptide strands that run in the same direction, meaning, the direction of their N-terminal and C-terminal ends is the same. Antiparallel beta sheets have peptide strands running in the opposite direction relative to one another.

The secondary structure of a protein is folded further into a conformation (arrangement of the backbone and side chains) that produces a compact, stable, and biochemically active polypeptide. This tertiary structure is the final structure of the individual polypeptide. It is formed by hydrogen bonds between both the backbone and the side chains and may be stabilized by additional covalent bonds between cysteines, which have a sulfur-containing R group. The covalent bonds between cysteine molecules are called disulfide bonds, also known as disulfide bridges. The tertiary conformation is also stabilized by interactions with the protein's environment. Hydrophobic, or water-avoiding, portions of the protein are located in the core of the protein, while hydrophilic, or water-loving, portions face its aqueous surroundings. Further, van der Waals forces, a type of electrostatic attraction, are also observed to play a role in the tertiary structures of proteins. These are weak attractive or repulsive forces that occur between molecules within close proximity of each other. They result from fluctuating charge densities of nearby molecules. Though relatively weak compared to the other forces involved in the formation of a tertiary protein structure, the large number of van der Waals interactions that occur within large protein molecules makes them a significant component of tertiary protein folding. Once a protein’s tertiary structure has been adopted, most proteins are functional.

Tertiary Structure Summary

Alpha-helices, or 𝛼-helices, and disulfide bonds are among the types of interactions between amino acids that contribute to tertiary structure. There are two classes of beta sheets, or 𝛽-sheets. Parallel beta sheets contain peptide strands that run parallel to one another. Antiparallel beta sheets contain peptide strands that run in opposite directions of each other.
Some protein structures consist of more than one individual polypeptide, or subunit. The quaternary structure, or arrangement of specific protein units, of such assemblies describes the arrangement of the protein subunits. The bonds responsible for the quaternary structure of proteins include hydrogen bonds, covalent and ionic bonds, hydrophobic interactions, and van der Waals forces, which are the weakest intermolecular forces that form because of attraction between molecules.

If a protein consists of only a single polypeptide chain, its tertiary structure is the highest level of structure needed to describe it. Many proteins, however, are made up of more than one polypeptide chain, and the quaternary structure describes how these protein subunits are assembled. In general a protein made up of a definite number of subunits is called an oligomer (where oligo- means "a few" and –mer means "units"). A protein that has two identical or similar subunits is called a dimer. One with three subunits is called a trimer, with four a tetramer, and so on. Filaments, which are long protein chains such as those found in hair, are of varying lengths and could in theory be infinitely long; they are often called polymers (poly- means "many").

Some large proteins are made of multiple copies of the same subunit, while in others the subunits are different. A dimer that consists of two of the same protein subunit is called a homodimer. The catabolite activator protein (CAP), which is a protein that regulates transcription in bacteria, is an example of a homodimer. In contrast, a dimer made of two different protein subunits is called a heterodimer.

Some proteins are composed of repeating sets of subunits. Hemoglobin, which is a protein in erythrocytes containing iron, facilitates the transport of oxygen by binding to it and is one such example of repeating sets of subunits. It is a heterotetramer, a four-subunit protein whose subunits are not identical. It is also called a dimer of dimers because it is assembled from two sets of two different polypeptides. Every subunit of hemoglobin is a globular protein with a heme group, which consists of one iron atom that binds with one oxygen molecule.

Human Hemoglobin

The oxygen-carrying ability of red blood cells relies on human hemoglobin, a globular protein. The heme groups are the flat structures with iron in the middle.

Roles of Proteins

Proteins play key roles in the structure, defense, transport, communication, movement, and chemical reactions in a living cell.

As the machinery of the cell, proteins perform many different roles in living organisms. Proteins are involved in cell and organism structure, movement, defense, transport of materials, cell communication, and biochemical functions.

For example, the protein tubulin is a structural protein of the cytoskeleton. It forms long polymeric filaments called microtubules, which are commonly called the "thick filaments" of the cytoskeleton. Microtubules help a cell maintain its structure and organize the cytoplasm. During cell division, microtubules form structures called mitotic spindles that separate the chromosomes of the dividing cell.

Protein Role Description Example
Structure
  • Make up cellular cytoskeleton
  • organize cytoplasm
Tubulin
Cell Division
  • Aid in chromosome separation
Mitotic spindles
Immunity
  • Antibodies recognize specific antigens in immune defense
Immunoglobulin A
Transport
  • Transport of oxygen in blood
  • cell membrane proteins for facilitated diffusion and active transport
Hemoglobin
Hormone
  • Chemical signals released by endocrine glands that induce an organ/tissue response
Insulin
Cell Signaling
  • Second messengers within a cell inducing intracellular response to extracellular cues
Cyclic adenosine monophosphate (cAMP)
Motion
  • Provide cellular movement in the form of flagella/cilia or organism movement in the form of muscles
Actin/myosin

At the organism level, the protein collagen is an important structural protein. It is a long, fibrous material consisting of three polymeric protein chains twisted into a triple helix. Collagen occupies the extracellular space, the fluid-filled spaces in an organism between cells. It is part of flexible tissues, such as skin and ligaments, or more rigid ones, such as cartilage and bone.

Other proteins are part of an organism's defense system. Proteins called immunoglobulins are antibodies made by white blood cells (B cells), part of the immune system. A single antibody consists of four separate polypeptide chains: two smaller "light" chains and two "heavy" chains. Some antibodies are secreted into the blood, and some are membrane proteins that remain on the surface of a B cell. Each antibody recognizes a specific antigen, or foreign molecule, allowing the organism to defend against that antigen.

Proteins are integral in material transport, which may take place either from one place to another within an organism, such as the transport of oxygen by the protein hemoglobin, or into and out of cells. The plasma membrane of a cell, a phospholipid bilayer surrounding the cell, is impermeable to the aqueous environment surrounding the cell. However, the cell sometimes needs to allow hydrophilic, lipid insoluble substances to pass through the plasma membrane. In these cases, proteins such as ion channels and carrier proteins form pores in the plasma membrane and can selectively allow these substances to pass through. Such a protein is folded so that it has a hydrophobic part facing the plasma membrane and a hydrophilic part forming a central pore. Once the substance passes through, it is released into the cytoplasm.

Facilitated Diffusion in Cells

Lipid insoluble, highly polar, or very large molecules would not be able to pass through cell membranes without the aid of carrier proteins through a process called facilitated diffusion. This mechanism allows molecules to pass through the lipid layer.
Proteins form both the signal molecules and the receptor molecules needed for cell communication. Insulin is a small molecule that is made of two short polypeptide chains and is produced by the pancreas and released into the bloodstream. When insulin binds to the insulin receptor protein, which is embedded in the plasma membranes of all mammalian cells, it triggers those cells to take up glucose from the blood. Failures of this signaling system result in the disease diabetes.

Motion in cells is also the task of proteins. The proteins actin and myosin work together in many different cell contexts to allow cells and organisms to move. In animals, polymeric filaments of actin and fibers of myosin are the main components of muscle cells. These two main types of filaments slide past each other to allow for muscle contraction. In nonmuscle cells, smaller assemblies of actin and myosin filaments perform other tasks requiring motion, notably the separation of cells at the end of mitosis by means of a contractile ring.