A recurring theme in biology is that structure is related to function. This theme is particularly important in understanding proteins. Humans have tens of thousands of different proteins and each has a specific structure and function. Despite the diversity of proteins, they are all constructed from the same 20 amino acids. Different proteins have different sequences of these 20 amino acids.
The sequence of amino acids in a protein is referred to as its primary structure. The secondary structure of a protein refers to regions of the molecule that are coiled or folded (α helices or β pleated sheets) due to hydrogen bonds between amino acids. Tertiary structure refers to the overall shape of the protein due to interactions between the side chains (R groups) of the amino acids. Some proteins are made of more than one polypeptide chain – the aggregation of these polypeptide chains refers to a protein’s quaternary structure. A change in a protein’s primary structure results in a change in the overall structure of the protein.
Sickle-cell is a genetic disease that results in the abnormal production of the protein hemoglobin which causes misshapen red blood cells. The abnormality is in the 6th position of the β subunit of the molecule. Normal hemoglobin has a glutamic acid while sickle-cell hemoglobin has a valine in the 6th position. The presence of the valine causes hemoglobin molecules to aggregate together into rod formations. These rods of hemoglobin are not effective at carrying oxygen. People with sickle-cell anemia suffer episodes of “sickle-cell crises” which are painful and, left untreated, can lead to death.
Refer to the figure below and use your understanding of the chemical behavior of the R groups to predict what would happen if the glutamic acid in the 6th position of the β subunit was replaced with an aspartic acid (instead of valine). Would this cause more or less disruption to the function of the resulting hemoglobin?