Protein folding

Protein folding is the physical process by which a protein, after synthesis by a ribosome as a linear chain of amino acids, changes from an unstable random coil into a more ordered three-dimensional structure. This structure permits the protein to become biologically functional or active. The folding of many proteins begins even during the translation of the polypeptide chain. The amino acids interact with each other to produce a well-defined three-dimensional structure, known as the protein's native state. This structure is determined by the amino-acid sequence or primary structure. The correct three-dimensional structure is essential to function, although some parts of functional proteins may remain unfolded, indicating that protein dynamics are important. Failure to fold into a native structure generally produces inactive proteins, but in some instances, misfolded proteins have a modified or toxic functionality. Several neurodegenerative and other diseases are believed to result from the accumulation of amyloid fibrils formed by misfolded proteins, the infectious varieties of which are known as prions. Many allergies are caused by the incorrect folding of some proteins because the immune system does not produce the antibodies for certain protein structures. Denaturation of proteins is a process of transition from a folded to an unfolded state. It happens in cooking, burns, proteinopathies, and other contexts. Residual structure present, if any, in the supposedly unfolded state may form a folding initiation site and guide the subsequent folding reactions. The duration of the folding process varies dramatically depending on the protein of interest. When studied outside the cell, the slowest folding proteins require many minutes or hours to fold, primarily due to proline isomerization, and must pass through a number of intermediate states, like checkpoints, before the process is complete. On the other hand, very small single-domain proteins with lengths of up to a hundred amino...