When a point mutation on the DNA strand creates a premature stop codon the RNA template will not be completely translated, resulting in a protein with a lower molecular weight due to fewer amino acid residues. As a result, the protein will also likely be nonfunctional. This is an example of a nonsense point mutation.

A slightly altered protein with the same molecular weight would be an example of a missense point mutation, resulting in the substitution of one amino acid for another.

Denaturation of a protein means that the structure of the protein has changed, rendering it non-functional. The presence of an enzyme can alter the structure of a substrate protein, but is only likely to affect a small region of the protein structure. In contrast, most denaturing processes involve environmental changes that affect the protein as a whole.

A drop in pH can cause denaturation, as it can de-protonate or re-protonate the protein causing a conformational change. This results in changes in the polar structure of the amino acid and can lead to hydrophobic shifts in tertiary structure to decrease functionality. Change in basicity can cause denaturation for the same reason, since this is essentially an increase in pH. Temperature change can also cause denaturation by disrupting internal bonds of the protein used to create secondary and tertiary structure.

Note that primary structure is not affected by denaturation, which is why proteins can re-fold and regain function after denaturation.

There are four levels of protein structure. Primary structure involves the linear arrangement of amino acids. It is simply the linear sequence of amino acids created by the ribosome during translation. Secondary structure involves the hydrogen bonding of the backbone and can form alpha-helices and beta-pleated sheets. Tertiary structure involves the interaction between amino acid side chains, or R-groups. These interactions can be hydrogen bonds, hydrophobic interactions, or disulfide bridges. Quaternary structure involves the interaction between two or more folded subunits, and is not present in every protein structure.

The primary structure of a protein is a linear sequence of amino acids. Amino acids are joined by peptide bonds between the N terminus of one amino acid and the C terminus of another amino acid through a condensation reaction, which results in the release of a water molecule. 

The secondary structure of protein folding is two-dimensional and can take two forms: alpha helices and beta-pleated sheets. The secondary structure is characterized by hydrogen bonds between peptide groups.

The tertiary structure of protein folding has a polypeptide chain backbone and a number of protein secondary structures: alpha helices and beta-pleated sheets. The tertiary structure is three-dimensional. The protein folding that causes the formation of the tertiary structure is influenced by hydrophobic interactions, disulfide bridges, hydrogen bonds, and salt bridges that create hydrophobic and hydrophilic regions.

The protein quaternary structure is the highest level of protein architecture and refers to the arrangement of protein subunits and their interactions with one another. There is a range in the complexity in the quaternary structure of proteins from dimers, such as DNA polymerase, to tetramers, such as hemoglobin. These structures are always composed of more than one protein subunit.

Disruption of normal protein folding or denaturation—protein unfolding—occurs under certain environmental conditions. Denaturation is defined as the loss of quaternary, tertiary, and secondary folding through the disruption of protein subunits and bonds. The environmental conditions that cause denaturation include the following: extreme temperatures, chemical interference, and extreme pH levels. Denatured proteins may sometimes refold if conditions stabilize; however, this does not typically happen.

Cells have certain mechanisms to protect proteins from denaturation and ensure proper folding. The cell uses two mechanisms to protect proteins: chaperones and heat shock proteins. Chaperones are a large class of proteins that aid with protein folding and prevent folding defects under normal and stressed conditions, during which chaperone expression is up regulated. Chaperones use ATP to induce a conformational change to provide an isolated environment for the protein to fold and prevent protein aggregation. Heat shock proteins are only produced under stress conditions. Heat shock proteins have a variety of functions including functioning as a chaperone, aiding in the binding of immune antigens, and preventing platelet aggregation in the cardiovascular tract. 

Aggregations of misfolded proteins contribute to degenerative diseases such as Alzheimer’s, Huntington’s, and Parkinson’s diseases. Protein misfolding and degradation lead to protein-related diseases, such as cystic fibrosis.