Protein structure

Lore & Background

Proteins are polymers, specifically polypeptides, formed from sequences of amino acids, which are the monomers of the polymer. A single amino acid monomer may also be called a residue, indicating a repeating unit of the polymer. By convention, a chain under 30 amino acids is often identified as a peptide rather than a protein. Protein structures range in size from tens to several thousand amino acids, and by physical size, they are classified as nanoparticles between 1 and 100 nanometers. Very large protein complexes can be formed from protein subunits; for example, many thousands of actin molecules assemble into a microfilament. To perform their biological function, proteins fold into one or more specific spatial conformations driven by non-covalent interactions, including hydrogen bonding, ionic interactions, Van der Waals forces, and hydrophobic packing. A protein usually undergoes reversible structural changes in performing its function, with alternative structures referred to as different conformations and transitions between them called conformational changes. The primary structure is the sequence of amino acids in the polypeptide chain, held together by peptide bonds made during protein biosynthesis. The two ends of the chain are the carboxyl terminus (C-terminus) and the amino terminus (N-terminus), with residue counting starting at the N-terminal end. The primary structure is determined by the gene; a specific sequence of nucleotides in DNA is transcribed into mRNA, which is read by the ribosome in translation. Frederick Sanger discovered the sequence of amino acids in insulin, establishing that proteins have defining amino acid sequences. The sequence is unique to a protein and defines its structure and function. Post-translational modifications, such as phosphorylations and glycosylations, are usually considered part of the primary structure and cannot be read from the gene. Secondary structure refers to highly regular local sub-structures on the polypeptide backbone chain, with two main types—the α-helix and the β-strand or β-sheet—suggested in 1951 by Linus Pauling. These are defined by patterns of hydrogen bonds between main-chain peptide groups and have regular geometry constrained to specific dihedral angles on the Ramachandran plot. Tertiary structure is the three-dimensional structure of a single polypeptide chain, which may include one or

Reader's Guide

Protein structure is fundamental to understanding biological function at a molecular level. The four levels—primary, secondary, tertiary, and quaternary—describe the organization from amino acid sequence to complex multimers. Secondary structures like α-helices and β-sheets were suggested by Linus Pauling. Tertiary structure involves folding driven by hydrophobic interactions and stabilized by disulfide bonds and salt bridges. Quaternary structure involves aggregation of subunits, such as the heterotetramer of hemoglobin. Domains, motifs, and folds are recurring structural units. Protein dynamics involve transitions between conformational states on nanoscales, linked to allosteric signaling and enzyme catalysis. Structural biology employs techniques like X-ray crystallography, NMR spectroscopy, and cryo-electron microscopy to determine these structures.

Did You Know?

• A chain under 30 amino acids is often identified as a peptide rather than a protein.
• The primary structure of insulin was discovered by Frederick Sanger.
• Very large protein complexes can be formed from protein subunits, such as actin molecules assembling into a microfilament.