BIO - Proteins [LESSON]

Proteins

Proteins are among the most abundant organic molecules in living systems and are way more diverse in structure and function than other classes of macromolecules. A single cell can contain thousands of proteins, each with a unique function. Although their structures, like their functions, vary greatly, all proteins are made up of one or more chains of amino acids. Amino acids are the monomers that make up proteins. Each amino acid has the same fundamental structure, which consists of a central carbon atom bonded to an amino group (NH2), a carboxyl group (COOH), and to a hydrogen atom. You will often see them as -NH3+ and -COO- because, in the aqueous environment of the cell, both the amino group and the carboxyl group are ionized under physiological conditions.

Image shows an amino acid made of an amino group, a central atom with a hydrogen +  R-group attached, + a carboxyl group

Every amino acid also has another atom or group of atoms bonded to the central atom known as the R group. This R group, or side chain, gives each amino acid specific characteristics, including size, polarity, and pKa. The image below shows all 20 eukaryotic amino acids with the R groups shown in blue. Note that the backbone of each amino acid is exactly the same and the only piece that is different is the R group. The R groups have varying properties depending on their size and charge, which is what allows the protein to fold into different shapes depending on the order of amino acids (which is determined by the DNA code).

The image shows the 20 amino acids found in eukaryotes.

 

Here, we will look at the structure of proteins and how the sequence of amino acids determines how the protein folds up into 3-dimensional space.  Remember that the order of amino acids is determined by the DNA code – but we will learn more about how that information is passed along during transcription and translation in the molecular genetics unit. Each protein has a unique sequence and thus a unique 3-dimensional shape (conformation) that allows the function to be carried out. Remember, if there is an issue in the structure (environmental factor, mutation, etc) then there can be a loss of function. The image below shows each of the four levels of protein folding. It is useful to know that these do not happen sequentially. Rather, the protein folds up into these different structures simultaneously as it’s being created by the ribosome.

The image shows the four levels of protein folding.

Primary Structure

A protein's primary structure is the unique sequence of amino acids in each polypeptide chain that makes up the protein. The sequence and the number of amino acids ultimately determine the protein's shape, size, and function. Each amino acid is attached to another amino acid by a covalent bond, known as a peptide bond. When two amino acids are covalently attached by a peptide bond, the carboxyl group of one amino acid and the amino group of the incoming amino acid combine and release a molecule of water. As you saw in the last lesson, any reaction that combines two monomers in a reaction that generates H2O as one of the products is known as a dehydration synthesis reaction, so peptide bond formation is an example of a dehydration reaction.

The image shows two amino acids next to each other.

The sequence of a protein is determined by the DNA of the gene that encodes the protein. A change in the gene's DNA sequence may lead to a change in the amino acid sequence of the protein. Even changing just one amino acid in a protein’s sequence can affect the protein’s overall structure and function.

The image shows green circles for each amino acid stacked linearly to represent primary structure.

Secondary Structure

Secondary structure refers to local folded structures that form within a polypeptide due to interactions between certain atoms of the backbone. The most common types of secondary structures are the α helix and the β pleated sheet. Both structures are held in shape by hydrogen bonds, which form between the C=O of one amino acid and the H on the amino group of another (typically about four amino acids away from each other).

The image shows the overall folded structure of the B sheet and the spiral shape of the alpha helix.

Tertiary Structure

The tertiary structure of a polypeptide chain arises due to interactions between polar, nonpolar, acidic, and basic R groups within the polypeptide chain. When protein folding takes place in the aqueous environment of the body, the hydrophobic R groups of nonpolar amino acids are pushed into the interior of the protein, while the hydrophilic R groups lie mostly on the outside. Once the protein starts to fold due to these hydrophobic interactions, other R groups will interact. There are four potential interactions between R groups in the tertiary structure (please remember that this is overly simplified and not every interaction occurs in the same way) that are shown in the image below.

The image shows the possibilities of bonding in tertiary structure.

One note about the image above – the hydrophobic interactions between two nonpolar R groups are stabilized by van der Waals interactions. These are intermolecular forces present in all matter but are only significant in nonpolar interactions as there are no other forces present. See Lesson 1 for additional information.

Quaternary Structure

If a protein is part of a larger set of proteins, it is said to be a quaternary structure protein, but not all proteins display this. This means that the larger complex has multiple subunits that function together to perform the job of the protein. A couple of interesting examples of quaternary structure proteins include hemoglobin (with four subunits) and ATP synthase (with 6 subunits).

Please watch the video below and take detailed notes to understand how proteins fold into their 3-dimensional conformation according to their primary sequence of amino acids. The portion at the end regarding enzyme proteins will be very important in your very next lesson as well. 

Watch the video Macromolecules - Protein Structure and Function below.

Based on what you learned in this lesson, complete the Protein Folding Simulation below by first thinking about the right answer for each blank and then selecting the blank to reveal the correct answer. Then, select the arrow to move to the next stage of the simulation.

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