MAP2 and tau (orange) bind along microtubule protofilaments (blue).

Microtubule (MT) assembly is a dynamic process involving the addition and removal of tubulin αβ heterodimers. The binding of microtubule-associated proteins (MAPs) to MTs helps to prevent depolymerization of assembled filaments. Despite years of study, there has been little consensus on the structural basis for this stabilization. Open a number of textbooks on the subject, and you are likely to find that some show MAP proteins wrapping around the microtubule, binding together the protofilaments, while others picture MAPs binding lengthwise along individual protofilaments.On page 1187, Al-Bassam et al. finally resolve the structural basis for MAP stabilization of microtubules by examining the MAP2/tau family. Stabilization of MTs by MAP2/tau proteins is required during axon and dendrite development. Although both MAP2 and the COOH terminus of tubulin with which it interacts are unstructured in solution, upon binding, the complex condenses into an ordered form that the group could visualize by cryo-electron microscopy and image analysis.

Their results demonstrate that MAP2 binds lengthwise, along the outer ridge of microtubule protofilaments. This arrangement probably stabilizes microtubules by preventing the outward curling of tubulin subunits at the end of protofilaments (which occurs during depolymerization), rather than knitting protofilaments together.

The structural data also uncovered sequence-specific binding of MAP2 to tubulin monomers. MAP2 consists of three MT-binding repeats, which vary slightly in sequence, separated by spacer repeats. These repeats preferentially targeted either α or β monomers. Possibly the central repeat, which binds to tubulin most strongly, determines the alignment of the MAP on the protofilament by binding either α or β, with the outer repeats falling to the nearby monomers. ▪