Proteins perform the vast majority of biological work, acting as enzymes, structural components, and signaling agents in every living cell. These large molecules are built from smaller units called amino acids, which serve as the fundamental monomers of protein structure. There are 20 common types of amino acids. The specific sequence in which they are linked determines the unique function and three-dimensional shape of the final protein. The formation of these long chains requires a specific chemical bond to join the amino acids into a continuous polymer.
The Peptide Bond
The covalent bond that links two amino acids together to form a protein chain is known as the peptide bond, which is a specific type of amide linkage. This bond forms between the carboxyl group (\(\text{–COOH}\)) of one amino acid and the amino group (\(\text{–NH}_2\)) of the adjacent amino acid. The resulting structure is a \(\text{C-N}\) bond characterized by a carbonyl group (\(\text{C=O}\)) and an amide nitrogen (\(\text{N-H}\)), creating the repeating backbone of the protein.
A defining feature of this linkage is its partial double-bond character, which arises from the delocalization of electrons across the carbon, oxygen, and nitrogen atoms. This resonance effect gives the peptide bond stability and rigidity greater than a typical single bond. The partial double-bond nature restricts rotation around the \(\text{C-N}\) bond, forcing the atoms involved to lie in a single, fixed plane. This planar and rigid structure is foundational, influencing how the growing protein chain can fold into its three-dimensional structures.
The partial double-bond character also results in a shorter \(\text{C-N}\) bond length, further contributing to the stability of the protein backbone. The preferred configuration of the peptide bond is the trans isomer, where the adjacent \(\text{C}\alpha\) (alpha carbon) atoms are positioned on opposite sides of the bond. This trans arrangement is favored because it minimizes steric hindrance between the side chains of the neighboring amino acids.
The Chemical Reaction That Forms the Bond
The process by which the peptide bond forms is called dehydration synthesis, also known as a condensation reaction. This process involves the removal of a water molecule (\(\text{H}_2\text{O}\)) during bonding. Specifically, the hydroxyl group (\(\text{–OH}\)) is removed from the carboxyl group of the first amino acid, and a hydrogen atom (\(\text{–H}\)) is removed from the amino group of the second amino acid.
The remaining carbon atom from the carboxyl group then covalently links with the nitrogen atom from the amino group, forming the peptide bond and releasing \(\text{H}_2\text{O}\) as a byproduct. This synthesis process is endergonic, meaning it requires an input of energy, typically supplied by the cell in the form of adenosine triphosphate (ATP). The controlled formation of these bonds in living systems is catalyzed by complex enzymatic machinery, such as the ribosome during protein synthesis.
This bond formation reaction is the opposite of hydrolysis, a process used to break down proteins into their individual amino acid components. Hydrolysis involves the addition of a water molecule to the peptide bond. The water molecule effectively reverses the synthesis reaction, cleaving the covalent bond and restoring the carboxyl and amino groups on the separated amino acids.
Building the Polypeptide Chain
The repeated formation of peptide bonds creates a long, unbranched chain of amino acids called a polypeptide. The specific, linear sequence of amino acids in this chain is known as the primary structure of the protein. The chain has a distinct orientation, or directionality, because the peptide bond always forms in the same manner, leaving different chemical groups free at the two ends.
One end of the chain is characterized by a free amino group (\(\text{–NH}_2\)), referred to as the N-terminus. The other end is defined by a free carboxyl group (\(\text{–COOH}\)), known as the C-terminus. By convention, the amino acid sequence of a protein is always read and written starting from the N-terminus and proceeding toward the C-terminus.
This directionality is significant because it reflects the way proteins are synthesized in the cell, with new amino acids being added sequentially to the C-terminus of the growing chain. While the peptide bonds establish this primary structure, the final, functional shape of a protein is achieved through subsequent folding driven by interactions between the amino acid side chains. Polypeptide chains containing more than 50 amino acid units are generally classified as proteins.