The three-dimensional structure of proteins plays and important role in their function. The shape of a protein is typically described using four levels of structural complexity: the primary, secondary, tertiary, and quaternary structural levels.

Protein Primary Structure

The
primary structure of a protein is its amino acid sequence. Each protein has a unique amino acid sequence, and the unique order in which the amino acids are linked together determined the higher levels of structural organization. The primary structure of the α-subunit of human hemoglobin is shown below.

Primary Structure of the alpha subunit of hemoglobin


Q1. What are the first 10 amino acids in this polypeptide chain? What are the three letter codes for these amino acids?


Protein Secondary Structure

In most cases the polypeptide chain of a protein does not exist as an extended chain of amino acids. Instead amino acids adjacent to one another interact to form segments with defined structure. These local structural elements comprise the
secondary structure of a protein. The most common secondary structure elements are the α-helix and the β-pleated sheet. The α-helix and the β-pleated sheet are regular secondary structure elements since the Φ and Ψ angles within each element remains the same (or almost the same). Some segments do not have similar Φ and Ψ angles for all amino acids in the segment. Such segments are sometimes referred to as random coil regions. Random coil does not (necessarily) mean that the amino acids within this region take on random conformations from protein to protein (i.e. that the segment is highly flexible). Rather, random coil implies dissimilar Φ and Ψ angles within the segment.


into the JMol window (left). The molecule is shown using the 'cartoon' rendering scheme and is colored to show the various secondary structure elements. Rotate the molecule around and observe the distribution of secondary structures in the α-subunit of human hemoglobin.

residues 53-71. It can be seen that these 19 residues interact with each other to form an α-helical secondary structure element. Similarly each of the other secondary structure elements present in the protein is composed of residues that are adjacent to each other in sequence.

The
α-subunit of human hemoglobin is a predominantly helical protein.

on the other hand is an example of a protein with both helical and sheet secondary structures. The molecule is colored to show the various secondary structure elements. Rotate the molecule around and familiarize your self with the protein and its structure.

Q2. How many β-sheets does bovine ribonuclease have? How many β-strands are present in each of these sheets?

Let's examine two strands of the first sheet.

(1). Notice that, although the two strands highlighted in blue are part of the same sheet, and lie next to each other, they are formed from residues that are quite far apart in the protein sequence. 35-36 residues separate the two β-strands. Although the two β-strands are located in different areas of the protein
each strand is composed of residues that lie adjacent to each other (and thus conforms to the definition of a secondary structure element).

Q3. What forces are responsible for maintaining the structure of α-helices and β-sheets?


Protein Tertiary Structure

In a protein secondary structures are not found isolated from each other within an extended polypeptide chain. Instead secondary structure element interacts with each other giving rise to a compact and folded polypeptide chain. The relative orientation of secondary structure elements with respect to each other determines the overall three-dimensional shape of the polypeptide chain and is unique to a given protein. This overall three-dimensional structure of a protein, in which the relative orientations of all the secondary structure elements are taken into consideration, is called the tertiary structure of the protein.

Rotate the model of ribonuclease and observe how the different secondary structures interact with one another. This organization represents the tertiary structure of ribonuclease and is conserved in all ribonuclease proteins.

Reload the
α-subunit of human hemoglobin (link above) and observe its tertiary structure. Observe how the helices are arranged with respect to each other.

Q4. What forces are responsible for maintaining the tertiary structure of proteins?


Protein Quaternary Structure

The functional entity of some proteins are composed of more than one polypeptide chain. Human hemoglobin is such as example. The functional hemoglobin molecule is composed of four individual polypeptides chains, two of which are designated as α-chains and two of which are designated β-chains.

Rotate the molecule around and observe the arrangement and structure of the different chains.

The two -chains are identical to each other and the two -chains are identical to each other. The -chains are similar in structure to the -chains but are not identical. Each polypeptide chain is referred to as a subunit of the protein. Thus hemoglobin has four subunits. The number subunits and the manner in which they interact with each other is described by the
quaternary structure of the protein.


Q4. Which structural levels are found in all proteins?