Protein folding

Protein folding is the physical process where a protein chain is translated into its native three-dimensional structure, typically a "folded" conformation, by which the protein becomes biologically functional. Via an expeditious and reproducible process, a polypeptide folds into its characteristic three-dimensional structure from a random coil. Each protein exists first as an unfolded polypeptide or random coil after being translated from a sequence of mRNA into a linear chain of amino acids. At this stage, the polypeptide lacks any stable (i.e., long-lasting) three-dimensional structure (see the left side of the first figure). As the polypeptide chain is being synthesized by a ribosome, the linear chain begins to fold into its three-dimensional structure. 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, the folded protein (see the right side of the figure), known as the native state. The resulting three-dimensional structure is determined by the amino-acid sequence or primary structure (e.g., Anfinsen's dogma). 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 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.