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Circular dichroism (CD) and NMR experiments have shown that each mutated CAP-gly domainof the [p150.sup.Glued] subunit of the dynactin complex is folded but less stable than the wild-type (WT) domain. The studies have shown that the disease-associated, point mutations have affected the stability of the domain and have inhibited their interaction with EB1 but have not inhibited their interaction with microtubules.

Point mutations within the CAP-gly domain of the p150Glued subunit of the dynactin complex have been identified in patients with distal spinal bulbar muscular atrophy (dSBMA) and Perry's syndrome. Herein, we show by CD and NMR experiments that each mutated CAP-gly domain is folded but less stable than the wild-type (WT) domain. We also demonstrate that the domains harboring these mutations bind to microtubules but fail to bind to EB1. These data indicate that these disease-associated, point mutations affect the stability of this domain and inhibit their interaction with EB1 but do not inhibit their interaction with microtubules. [ABSTRACT FROM AUTHOR]