Disease-associated mutations in the p150(Glued) subunit destabilize the CAP-gly domain.
Point mutations within the CAP-gly domain of the p150(Glued) 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.
Department of Molecular Medicine, Beckman Research Institute at City of Hope, Duarte, California 91010, USA.
Shubbir
S
Ahmed
Shangjin
S
Sun
Amanda E
AE
Siglin
Tatyana
T
Polenova
John C
JC
Williams
D002942:Circular Dichroism; D000072159:Dynactin Complex; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000235:genetics*; D020966:Muscular Disorders, Atrophic / Q000235:genetics*; D019906:Nuclear Magnetic Resonance, Biomolecular; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D013577:Syndrome
C000606360:DCTN1 protein, human; D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins