Which factor directly determines the primary structure of a protein?

• A. The overall 3D folding driven by interactions among side chains (hydrophobic effect, ionic interactions, and disulfide bonds)
• B. The pattern of hydrogen bonding between backbone groups that forms $\alpha$-helices and $\beta$-sheets
• C. The association of multiple polypeptide subunits into a functional oligomer
• D. The linear sequence of amino acids encoded by the gene (DNA) and translated into the polypeptide

Answer: (D)

Verified step by step guidance

1. Understand that the primary structure of a protein refers to the linear sequence of amino acids in the polypeptide chain.
2. Recognize that this sequence is directly determined by the genetic information encoded in the DNA, which is transcribed into mRNA and then translated into the amino acid chain.
3. Note that the other options describe higher levels of protein structure: secondary structure involves hydrogen bonding forming alpha-helices and beta-sheets; tertiary structure involves 3D folding driven by side chain interactions; quaternary structure involves the assembly of multiple polypeptide subunits.
4. Therefore, the factor that directly determines the primary structure is the specific order of amino acids as dictated by the gene sequence.
5. Summarize that the primary structure is foundational because it ultimately influences all higher levels of protein structure and function.