Understanding Protein Structure: Primary, Secondary, Tertiary, and Quaternary
Protein Structure and Function
“Structure equals function” is the basic tenet of Protein Modeling: i.e., it’s important to know what a protein’s structure is like because its function is determined by its structure.
There are four different types of protein structure: primary, secondary, tertiary, and quaternary.
Primary Structure
Primary structure is the sequence of amino acid residues in a protein chain. They’re called residues because they’re not individual amino acids anymore, having lost a hydrogen off their amino groups and a hydroxide ion off their carboxylic acid groups in the process of bonding through dehydration synthesis. In short, the ends of the amino acids are missing because they’re connected, so we call them “residues” instead of “amino acids”. There are 20 main varieties of amino acid, which differ only in their sidechain (sometimes called an “R group”).
Different residue sidechains have different properties; for example, some sidechains are negatively charged, and some are positively charged. These properties determine how the protein folds (i.e., the secondary and tertiary structure), because certain types of residues attract, repel or bond to other types of residues. Also, the types of residues present can determine how the protein interacts with other molecules such as DNA – for example, serine can form hydrogen bonds, and therefore is often found at binding sites in a protein.
Charged sidechains repel like charges and attract opposite charges. Hydrophilic, or polar, sidechains usually end up on the outside of a folded structure, because most proteins fold in a watery environment and the polar sidechains interact well with water, which is also polar. For the same reason, hydrophobic, or non-polar, sidechains usually end up on the inside of the structure, because they do not interact well with water. Cysteine forms very strong covalent disulfide bonds with other cysteines.
Each residue in a chain is given a number, starting at the amino terminus (the end that has an amino group still present) with the lowest number (which is not always 1, depending on the numbering conventions for the particular family of proteins) and going up to the carboxy terminus (the end that has a carboxyl group still present).
Secondary Structure
Secondary structure is the first level of folding in a protein. Patterns called “motifs”, such as alpha helices and beta sheets (by far the two most common), are caused by hydrogen bonding between the backbone carbons (the central carbons of amino acids, also known as alpha carbons) of the residues.
Alpha helices are slightly more common in proteins overall than beta sheets. These helices are tightly coiled single strands, kept in place by hydrogen bonds between nearby residues. They can be anywhere from only a few residues in length to over 100 Angstroms in some proteins. They tend to be the base of protein “stalks”.
Beta sheets, on the other hand, are made up of many beta strands – kinked sequences of residues separated by loops. These strands line up parallel to each other – actually, antiparallel, which means that adjacent strands point in opposite directions (direction matters, remember, because of the numbering of residues from the amino terminus to the carboxy terminus) – with multiple hydrogen bonds between adjacent strands. They are very strong as protective or support layers.
Tertiary Structure
Tertiary structure is the position in three dimensions of the secondary structures (motifs). It is determined by the secondary structures present, as well as the properties of the sidechains. Hydrophilic sidechains such as glutamine will move to the “outside” when the protein is folded in a watery environment, while hydrophobic sidechains such as tryptophan will cluster “inside” the protein, protected by other sections of the protein, to prevent their exposure to water. Oppositely charged sidechains come together, forming salt bridges (ionic bonds), while sidechains with the same charge repel each other. Cysteine, which contains sulfur, bonds covalently with other cysteines to form strong disulfide bonds. The interaction of all these attractions and repulsions cause the protein to develop a unique shape in 3D, called a “conformation”.
The protein’s tertiary structure also depends on the environment in which it is folded: in the human body, which is a watery environment, the hydrophobic (nonpolar) sidechains end up on the inside, as stated above. However, in a protein folded in a hydrophobic environment (such as a protein embedded in a phospholipid cell membrane), the hydrophilic (polar) sidechains end up on the inside.
Quaternary Structure
Quaternary structure is the arrangement of each of the individual pieces (monomers) of a multi-unit (multimeric) protein. These subunits, or “chains” as they are often called, each have their own amino and carboxy terminus, and are not physically attached to each other. However, they are held together by bonds – which can be disulfide or ionic, although more commonly the latter – and arranged together in a specific conformation. Multimers are quite common, and may contain several distinct chains or simply several copies of the same one (or few).
Further Reading:
- Protein Synthesis: Learn about the fascinating process of how proteins are made.
- Protein Structure Determination: Explore the techniques used to unravel the complex 3D structures of proteins.
- Cellular Functions of Proteins: Delve into the diverse roles proteins play in the cell, from enzymes to structural components.
This content provides a comprehensive overview of protein structure and function. For more detailed information, please refer to the linked resources and further research.