Intrinsic structural disorder in cytoskeletal proteins

Cytoskeleton, the internal scaffold of the cell, displays an exceptional combination of stability and dynamics. It is composed of three major filamentous networks, microfilaments (actin filaments), intermediate filaments (neurofilaments), and microtubules. Together, they ensure the physical and structural stability of the cell, whereby also mediating its large-scale structural rearrangements, motility, stress response, division, and internal transport. All three cytoskeletal systems are built upon the same basic design: they have a central repetitive scaffold assembled from folded building elements, surrounded and regulated by accessory regions/proteins that regulate its formation and mediate its countless interactions with its environment, serving to send regulatory signals to and from the cytoskeleton. Here, we elaborate on the idea that the opposing features of stability and dynamics are also manifest in the dichotomy of the structural status of its components, the core being highly structured and the accessory proteins/regions being highly disordered, and are responsible for most of the regulatory (post-translational) input promoting adaptive responses and providing dynamics necessary for each of the cytoskeletal systems. This pattern entails special consequences, in which the manifold functional advantages of structural disorder, most pronounced in regulatory and signaling functions, are all exploited by nature.