Disease-Associated Mutations in the p150Glued Subunit Destabilize the CAP-gly Domain
Copyright policy )Disease-Associated Mutations in the p150Glued 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.
- University of Delaware United States
- Beckman Research Institute United States
- City Of Hope National Medical Center United States
- Thomas Jefferson University United States
Circular Dichroism, Dynactin Complex, Syndrome, Muscular Disorders, Atrophic, Protein Structure, Tertiary, Humans, Point Mutation, Microtubule-Associated Proteins, Nuclear Magnetic Resonance, Biomolecular
Circular Dichroism, Dynactin Complex, Syndrome, Muscular Disorders, Atrophic, Protein Structure, Tertiary, Humans, Point Mutation, Microtubule-Associated Proteins, Nuclear Magnetic Resonance, Biomolecular
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