The Rules of Protein Structure

• The function of a protein is determined by its shape.
• The shape of a protein is determined by its primary structure (sequence of amino acids).
• The sequence of amino acids in a protein is determined by the sequence of nucleotides in the gene (DNA) encoding it.

• changes in pH (alters electrostatic interactions between charged amino acids)
• changes in salt concentration (does the same)
• changes in temperature (higher temperatures reduce the strength of hydrogen bonds)
• presence of reducing agents (break S-S bonds between cysteines)

None of these agents breaks peptide bonds, so the primary structure of a protein remains intact when it is denatured.

When a protein is denatured, it loses its function.

• A denatured enzyme ceases to function.
• A denatured antibody no longer can bind its antigen.

Often when a protein has been gently denatured and then is returned to normal physiological conditions of temperature, pH, salt concentration, etc., it spontaneously regains its function (e.g. enzymatic activity or ability to bind its antigen).

• the protein has spontaneously resumed its native three-dimensional shape
• its ability to do so is intrinsic; no outside agent was needed to get it to refold properly

In the cell, there are proteins, called molecular chaperones, that may enable a newly-synthesized protein to acquire its final shape faster than it otherwise would. But the rule still holds, what that final shape will be is determined by only one thing: the precise sequence of amino acids in the protein.

And the sequence of amino acids in every protein is dictated by the sequence of nucleotides in the gene encoding that protein. So the function of each of the thousands of proteins in an organism is specified by one or more genes.