Gain of function of immunoglobulins after partial unfolding or cofactor binding

Two recent articles in the Journal of Molecular Biology, provide strong evidence that certain intracellular proteins, mostly involved in the cellular signalling, acquire functional activity only after partial denaturation. Thus, non-native forms of such proteins acquire functional activity, while the native forms of the proteins are devoid of these activities. As described by Korzhniev (2013), the transition to non-native (non-ground state) conformer of a given protein can be induced by changes in the environment, post-translational modification, cofactor binding or spontaneous unfolding of the protein due to intrinsic thermal fluctuations. In this correspondence we would like to discuss another case of gain of functional activity of proteins after a shift from the native conformation to non-native conformation. Here we provide arguments that similar structure-function transitions may be typical for one of the most abounded plasma proteins--immunoglobulins.