Microtubule-associated proteins (MAPs) are essential for regulating and organising cellular microtubules (MTs). However, our mechanistic understanding of MAP function is limited by a lack of detailed structural information. Using cryo-electron microscopy (cryo-EM) and single particle algorithms, we solved the 8Å structure of doublecortin (DCX)-stabilized microtubules. Because of DCX's unusual ability to specifically nucleate and stabilize 13-protofilament (pf) MTs, our reconstruction provides unprecedented insight into the structure of MTs with their in vivo architecture and in the absence of a stabilizing drug. DCX specifically recognises 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 facilitates formation of 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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.