Disease-Associated Mutations in the p150Glued Subunit Destabilize the CAP-gly Domain

摘要

Point mutations within the CAP-gly domain ofnthe p150Gluednsubunit of the dynactin complex have beennidentified in patients with distal spinal bulbar muscularnatrophy (dSBMA) and Perry’s syndrome. Herein, we shownby CD and NMR experiments that each mutated CAP-glyndomain is folded but less stable than the wild-type (WT)ndomain. We also demonstrate that the domains harboringnthese mutations bind to microtubules but fail to bind tonEB1. These data indicate that these disease-associated,npoint mutations affect the stability of this domain andninhibit their interaction with EB1 but do not inhibit theirninteraction with microtubules.