The unique sequence for every protein is ultimately determined by the gene encoding the protein. A change in nucleotide sequence of the gene’s coding region may lead to a different amino acid being added to the growing polypeptide chain, causing a change in protein structure and function. In sickle cell anemia, the hemoglobin β chain (a small portion of which is shown in [link] ) has a single amino acid change, out of 600 total amino acids, causing a change in protein structure and function.
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 assume a crescent or “sickle” shape, which clogs arteries ( [link] ). 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 α -helix and β -pleated sheet structures ( [link] ).
Tertiary structure
The unique three-dimensional structure of a polypeptide is its tertiary structure ( [link] ). This structure is in part due to chemical interactions at work on the polypeptide chain. Primarily, the interactions among R groups creates the complex three-dimensional tertiary structure of a protein. The nature of the R groups found in the amino acids involved can counteract the formation of the hydrogen bonds described for standard secondary structures. For example, R groups with like charges are repelled by each other and those with unlike charges are attracted to each other. When protein folding takes place, the hydrophobic R groups of nonpolar amino acids lay in the interior of the protein, whereas the hydrophilic R groups lay on the outside. The former types of interactions are also known as hydrophobic interactions. Interaction between cysteine side chains forms disulfide linkages in the presence of oxygen, the only covalent bond forming during protein folding.
All of these interactions, weak and strong, determine the final three-dimensional shape of the protein. When a protein loses its three-dimensional shape, it may no longer be functional.