Name: how protein shape controls function
Uploaded: 2020-09-24T15:06:53.000Z
Duration: 2 min 15 s
Channel: JoVE

Proteins are polymers of amino acids linked together through peptide bonds. Most proteins fold into specific three-dimensional structures to perform their function.
Protein structure is classified into four categories: primary, secondary, tertiary, and quaternary.
The linear sequence of amino acids in the protein is its primary structure. These sequences are read in the polymer synthesis order, from the N-terminal, the free amino end, to the C-terminal, the free carboxyl end.
Secondary structures form through hydrogen bonding between the oxygen from the carbonyl group of one amino acid and the hydrogen from the amino group of another. Common secondary structures include &#945;-helices and &#946;-pleated sheets.&#160;
These and other connecting structures, such as &#946;-turns, further interact to form the protein&#8217;s three-dimensional structure, known as the tertiary structure.
The formation of the tertiary structure occurs due to interactions between the R-groups of the amino acids.
R-groups with opposite charges can form ionic bonds, and sulfur in two cysteines can form a covalent disulfide bridge. Other contributors include hydrophobic interactions between hydrophobic side chains and hydrogen bonds between polar side chains.
Additionally, some proteins form quaternary structures, assemblies of two or more polypeptide chains. For example, hemoglobin is a protein made up of four subunits, two &#945; and two &#946;.
Scientists can use the structure of a protein to predict its function and location in a cell. Proteins in the cell cytoplasm have hydrophilic amino acids on their surfaces that interact with the water in the cytoplasm and have hydrophobic cores.
In contrast, proteins present in cell membranes often have hydrophobic amino acids on the surface that interact with glycerophospholipids in the membrane and have hydrophilic cores.&#160;

protein and protein structure

Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein&#39;s shape is critical to its function. For example, an enzyme can bind a specific substrate at its active site. If this active site is altered because of local changes or changes in overall protein structure, the enzyme may be unable to bind to the substrate. To understand how the protein gets its final shape or conformation, we need to understand the four levels of protein structure: primary, secondary, tertiary, and quaternary.
Primary Structure
Amino acids&#39; unique sequence in a polypeptide chain is its primary structure. For example, the pancreatic hormone insulin has two polypeptide chains, A and B, and they are linked together by disulfide bonds. The N terminal amino acid of the A chain is glycine; whereas, the C terminal amino acid is asparagine.&#160; The amino acid sequences in the A and B chains are unique to insulin.
The gene encoding the protein ultimately determines the unique sequence for every protein. A change in the nucleotide sequence of the gene&#8217;s coding region may lead to adding a different amino acid to the growing polypeptide chain, causing a change in protein structure and function. In sickle cell anemia, the hemoglobin &#946; chain has a single amino acid substitution, causing a change in protein structure and function. Specifically, valine in the &#946; chain substitutes the amino acid glutamic acid. Because of this change of one amino acid in the chain, hemoglobin molecules form long fibers that distort the biconcave, or disc-shaped, red blood cells and causes them to assume a crescent or &#8220;sickle&#8221; shape, which clogs blood vessels. This can lead to myriad serious health problems such as breathlessness, dizziness, headaches, and abdominal pain for those affected by this disease.
Secondary Structure
The local folding of the polypeptide in some regions gives rise to the secondary structure of the protein. The most common are the &#945;-helix and &#946;-pleated sheet structures. Both structures are held in shape by hydrogen bonds. The hydrogen bonds form between the oxygen atom in the carbonyl group in one amino acid and another amino acid that is four amino acids farther along the chain.
Every helical turn in an alpha helix has 3.6 amino acid residues. The polypeptide&#39;s R groups (the variant groups) protrude out from the &#945;-helix chain. In the &#946;-pleated sheet, hydrogen bonding between atoms on the polypeptide chain&#39;s backbone forms the &#34;pleats&#34;. The R groups are attached to the carbons and extend above and below the pleat&#39;s folds. The pleated segments align parallel or antiparallel to each other, and hydrogen bonds form between the partially positive hydrogen atom in the amino group and the partially negative oxygen atom in the peptide backbone&#39;s carbonyl group. The &#945;-helix and &#946;-pleated sheet structures are in most globular and fibrous proteins, and they play an important structural role.
Tertiary Structure
The polypeptide&#39;s unique three-dimensional structure is its tertiary structure. This structure is in part due to chemical interactions at work on the polypeptide chain. Primarily, the interactions among R groups create the protein&#39;s complex three-dimensional tertiary structure. The nature of the R groups in the amino acids involved can counteract forming the hydrogen bonds we described for standard secondary structures. For example, R groups with like charges repel each other, and those with unlike charges are attracted to each other (ionic bonds). When protein folding takes place, the nonpolar amino acids&#39; hydrophobic R groups lie in the protein&#39;s interior; whereas, the hydrophilic R groups lie on the outside. Interactions between cysteine side chains form disulfide linkages in the presence of oxygen, the only covalent bond that forms during protein folding.
All of these interactions, weak and strong, determine the protein&#39;s final three-dimensional shape. When a protein loses its three-dimensional shape, it may no longer be functional.
Quaternary Structure
In nature, some proteins form from several polypeptides, or subunits, and the interaction of these subunits forms the quaternary structure. Weak interactions between the subunits help to stabilize the overall structure. For example, insulin (a globular protein) has a combination of hydrogen and disulfide bonds that cause it to mostly clump into a ball shape. Insulin starts out as a single polypeptide and loses some internal sequences in the presence of post-translational modification after forming the disulfide linkages that hold the remaining chains together. Silk (a fibrous protein), however, has a &#946;-pleated sheet structure that is the result of hydrogen bonding between different chains.
This text has been adapted from <a href="https://openstax.org/books/biology-2e/pages/3-4-proteins">Openstax, Biology 2e, Chapter 3.4: Proteins</a>.

Protein and Protein Structure

Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may ...

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how protein shape controls function

Proteins are a major class of organic molecules in living systems, and their shape helps determine what they do. They can act as structural, regulatory, contractile, or protective molecules. They also take part in transport, storage, membranes, toxins, and enzymes. All proteins are polymers of amino acids arranged in a linear sequence.

A protein’s function depends on its three-dimensional form. For example, an enzyme works when its active site can bind a specific substrate. If local changes or larger changes in protein structure alter that site, the enzyme may no longer bind the substrate. To understand how a protein reaches its final conformation, it helps to study four levels of structure: primary, secondary, tertiary, and quaternary.

Primary structure is the unique amino acid sequence of a polypeptide chain. In insulin, the pancreatic hormone, there are two polypeptide chains, A and B, held together by disulfide bonds. The A chain begins with glycine at the N terminus and ends with asparagine at the C terminus. The gene that encodes a protein determines this sequence, so a change in the coding region can add a different amino acid and change protein structure and function. Sickle cell anemia shows this clearly. In the hemoglobin beta chain, valine replaces glutamic acid, and that single change leads hemoglobin to form long fibers that distort red blood cells into a sickle shape and clog blood vessels. This can cause breathlessness, dizziness, headaches, and abdominal pain.

Secondary structure comes from local folding in parts of the polypeptide chain. The most common forms are the alpha helix and the beta-pleated sheet. Hydrogen bonds hold both forms in place. These bonds form between the oxygen in a carbonyl group on one amino acid and another amino acid four positions farther along the chain. In an alpha helix, each turn contains 3.6 amino acid residues, and the R groups point outward. In a beta-pleated sheet, hydrogen bonds form along the backbone to create pleats. The R groups extend above and below the folds, and the strands can align parallel or antiparallel. These structures are common in globular and fibrous proteins, where they provide support.

Tertiary structure is the full three-dimensional shape of one polypeptide. Interactions among R groups are the main force behind this folding. Like charges repel, unlike charges attract through ionic bonds, and hydrophobic R groups tend to move into the protein interior while hydrophilic R groups stay outside. Cysteine side chains can also form disulfide linkages in the presence of oxygen, and this is the only covalent bond formed during protein folding. Together, these weak and strong interactions set the final shape. If a protein loses that shape, it may no longer work.

Some proteins also form quaternary structure. This happens when several polypeptide subunits join together. Weak interactions between the subunits help stabilize the overall protein. Insulin is one example of a globular protein with hydrogen and disulfide bonds that help it form a mostly ball-like shape. It begins as a single polypeptide and then loses some internal sequences during post-translational modification after the disulfide linkages form and hold the remaining chains together. Silk is another example, but it is a fibrous protein with a beta-pleated sheet structure created by hydrogen bonding between different chains.

How Protein Shape Controls Function

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Explore how amino acid sequence, folding, and subunit interactions shape proteins. Learn the four levels of protein structure with insulin and sickle cell examples.

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How Protein Shape Controls Function

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