Conformational Transitions of 18.5-kilodaltons Myelin Basic Protein Studied by Fluorescence Spectroscopy and Forster Resonance Energy Transfer
The intrinsically-disordered, 18.5-kiloDalton (kDa) isoform of myelin basic protein (MBP) is a peripheral membrane protein that is essential to proper myelin formation in the central nervous system. MBP multifunctionality arises from its high conformational plasticity and its ability to undergo reversible disorder-to-order transitions. One such transition is the disorder-to-α-helical conformational change which is induced upon MBP-membrane binding. We have investigated the disorder-to-α-helical transition of MBP-derived α-peptides as well as of the full-length 18.5-kDa protein. The data suggest that the disorder-to-α-helical transition of MBP follows a three-state model: disordered↔intermediate↔α-helical, with each of the identified equilibrium states likely representing a conformational ensemble. The disordered state is characterized by slight compaction, whereas the intermediate globally more compact. This study suggests that multifunctionality in MBP could arise from differences in the population of energetically distinct ensemble clusters in different conditions and also provides an example of an IDP that undergoes cooperative global conformation change.