Binding Interactions with Tubulin's C-terminal Tail as Studied by Solution NMR

Abstract

Microtubules, formed by the polymerization of alpha and beta tubulin heterodimers, play an essential role in cell division and motility. The disordered C-terminal tails of each tubulin monomer are major sites of tubulin regulation. The post-translational modifications of the C-terminal tails enable microtubules to perform a wide range of functions, including the ability to control the dynamics and flexibility of microtubules as well as their ability to bind to microtubule-associated proteins (MAPs). Despite the importance of these C-terminal tails and their modifications, little structural information is available on how they affect binding to MAPs. Moreover, the functionality of the C-terminal tails may depend on whether the tail is attached to the ordered tubulin body or it is present as a free peptide. To address these limitations, we developed techniques to use solution nuclear magnetic resonance (NMR) as a probe of the C-terminal tails (Wall et al, ACS Chem Bio, 2016). Using this approach, we study interactions between the disordered C-terminal tails and different MAPs with a particular emphasis on how post-translational modifications may affect these binding interactions. Of particular interest to us are the +TIP families of MAPs, which localize to the growing end of microtubules.