Disordered proteins function as shock absorbers in axons

Synopsis

The human proteome is filled with disordered proteins. Typically protein function is associated with its structure, however in disordered proteins the lack of structure is necessary for their specific functions. The mechanical properties of one class of protein, neurofilaments (NF), are studied in a recent paper by Micha Kornreich, Eti Malka-Gibor, Ben Zuker, Adi Laser-Azogui, and Roy Beck at Tel Aviv University. NF self-assemble into a bottlebrush filament which forms the flexible skeleton of axons. Protruding disordered domains form a hydrogel network which allows for large compressions without damage to the neuron. The specific polypeptide sequence of the disordered regions exhibits interactions that are not governed by mean-field approximations of polymer physics-archive. Disordered domains are also present on the surface of other cytoskeletal elements, such as microtubules. This provides rationale for the role of disordered protein domains as flexible scaffolding elements in cellular structure.