Amino acids determine the function of proteins by dictating their three-dimensional structure; this structure then dictates the protein's biochemical function.
Proteins are complex molecules essential for virtually every biological process. Their functionality arises directly from their unique three-dimensional structures, which are, in turn, determined by the sequence of amino acids that compose them. This relationship can be summarized as: amino acid sequence → protein structure → protein function.
The Amino Acid Sequence: The Primary Structure
The sequence of amino acids, linked together by peptide bonds, constitutes the primary structure of a protein. Each amino acid possesses a unique side chain (R-group) with distinct chemical properties such as size, charge, hydrophobicity, and the ability to form hydrogen bonds. This sequence is genetically encoded in DNA and transcribed into mRNA, which is then translated by ribosomes to create the polypeptide chain.
Folding and Structure: From Sequence to Functionality
The amino acid sequence isn't just a linear chain; it folds into specific three-dimensional shapes due to interactions between the amino acid side chains. These interactions include:
- Hydrogen bonds: Form between polar side chains.
- Ionic bonds: Form between oppositely charged side chains.
- Van der Waals forces: Weak attractions between atoms.
- Hydrophobic interactions: Nonpolar side chains cluster together to avoid water.
- Disulfide bridges: Covalent bonds between cysteine residues.
These interactions lead to the formation of secondary structures (alpha-helices and beta-sheets), tertiary structure (overall 3D shape of a single polypeptide chain), and quaternary structure (arrangement of multiple polypeptide chains in a multi-subunit protein).
Structure Dictates Function
The final three-dimensional structure creates specific binding sites or active sites on the protein surface. The shape and chemical properties of these sites determine which molecules the protein can interact with and what kind of reaction it can catalyze. Examples include:
- Enzymes: Their active site specifically binds to a substrate, facilitating a chemical reaction. The precise arrangement of amino acids in the active site is crucial for catalysis.
- Antibodies: Their variable regions have specific shapes that allow them to bind to antigens, marking them for destruction.
- Receptors: Their binding sites recognize and bind to signaling molecules, triggering a cellular response.
- Structural proteins: Their shape and interactions with other proteins allow them to form cellular structures like filaments.
Consequences of Amino Acid Changes
Even a single amino acid change can drastically alter a protein's structure and function. This is because the new amino acid might have different chemical properties, disrupting the interactions that stabilize the protein's three-dimensional shape. For example, a mutation in hemoglobin that substitutes valine for glutamate causes sickle cell anemia due to incorrect folding and aggregation of the hemoglobin protein.
Sequence Similarity and Function Prediction
The principle that sequence determines structure and structure determines function allows scientists to predict the function of newly discovered proteins by comparing their amino acid sequence to those of known proteins. If two proteins share a high degree of sequence similarity, they are likely to have similar structures and perform similar functions, even if they are found in different organisms. As the provided reference states: "Because amino acid sequence determines protein structure and structure dictates biochemical function, proteins that share a similar amino acid sequence usually perform similar biochemical functions, even when they are found in distantly related organisms." This is a powerful tool in bioinformatics and proteomics.
