Roles of partly unfolded conformations in macromolecular self-assembly

From genes to cells there are many steps of hierarchical increments in building up complex frameworks that provide intricate networks of macromolecular interactions, through which cellular activities such as gene expression, signal processing, energy transduction and material conversion are dynamically organized and regulated. The self-assembly of macromolecules into large complexes is one such important step, but this process is by no means a simple aggregation of macromolecules with predefined, rigid complementary structures. In many cases the component molecules undergo either domain rearrangements or folding of disordered portions, which occurs only following binding to their correct partners. The partial disorder is used in some cases to prevent spontaneous assembly at inappropriate times or locations. It is also often used for finely tuning the equilibrium and activation energy of reversible binding. In other cases, such as protein translocation across membranes, an unfolded terminus appears to be the prerequisite for the process as an initiation signal, as well as the physical necessity to be taken into narrow channels. Self-assembly processes of viruses and bacterial flagella are typical examples where the induced folding of disordered chains plays a key role in regulating the addition of new components to a growing assembly. Various aspects of mechanistic roles of natively unfolded conformations of proteins are overviewed and discussed in this short review.