Template-free 13-protofilament microtubule-MAP assembly visualized at 8 Å resolution

Microtubule associated proteins (MAPs) are essential for regulating and organizing cellular microtubules (MTs) However, our mechanistic understanding of MAP function is limited by a lack of de tailed structural information Using cryo electron microscopy and single particle algorithms, we solved the 8 A structure of doublecortin (DCX) stabilized MTs Because of DCX's unusual ability to specifically nucleate and stabilize 13 protofilament MTs, our reconstruction provides unprecedented insight into the structure of MTs with an in vivo architecture, and in the absence of a stabilizing drug DCX specifically recognizes the corner of four tubulin dimers, a binding mode ideally suited to stabilizing both lateral and longitudinal lattice contacts A striking consequence of this is that DCX does not bind the MT seam DCX binding on the MT surface indirectly stabilizes conserved tubulin tubulin lateral contacts in the MT lumen, operating independently of the nucleotide bound to tubulin DCX's exquisite binding selectivity uncovers important insights into regulation of cellular MTs