Doublecortin engages the microtubule lattice through a cooperative binding mode involving its C-terminal domain.

ABSTRACT: Doublecortin (DCX) is a microtubule (MT)-associated protein that regulates MT structure and function during neuronal development and mutations in DCX lead to a spectrum of neurological disorders. The structural properties of MT-bound DCX that explain these disorders are incompletely determined. Here, we describe the molecular architecture of the DCX-MT complex through an integrative modeling approach that combines data from X-ray crystallography, cryo-electron microscopy, and a high-fidelity chemical crosslinking method. We demonstrate that DCX interacts with MTs through its N-terminal domain and induces a lattice-dependent self-association involving the C-terminal structured domain and its disordered tail, in a conformation that favors an open, domain-swapped state. The networked state ca

SUBMITTER: Rafiei A 

PROVIDER: S-EPMC9122500 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature