Intrinsically Disordered Protein: Difference between revisions

It has long been taught that proteins must be properly folded in order to perform their functions. This paradigm derives from work by

Christian B. Anfinsen and coworkers. In the 1960's, they showed that RNAse, when denatured so that 99% of its enzymatic activity was lost, could regain enzymatic activity within seconds when the denaturing agent was removed under proper conditions<ref>For the sake of brevity, this description is oversimplified. RNAse needed to be reduced to break disulfide bonds, as well as using 8 M urea, for denaturation. Oxidation without the denaturant then left an inactive enzyme because the disulfide bonds formed randomly, precluding proper folding except very slowly (many hours). Only when protein disulfide isomerase was added did the re-folding occur at a physiological rate (about a minute). The fact that RNAse could thus be trapped in an inactive conformation under physiological conditions contributed to the insights developed by Anfinsen and his team. Proteins lacking disulfides renatured in seconds. For details, see [http://nobelprize.org/nobel_prizes/chemistry/laureates/1972/anfinsen-lecexture.html Anfinsen's Nobel Lecture.]</ref>. They concluded that the amino acid sequence is sufficient for a protein to fold into its functional, lowest energy conformation. This work won the [[Nobel_Prizes_for_3D_Molecular_Structure|1972 Nobel Prize]], and was subsequently confirmed and extended by many researchers.