Work

Disease-Associated Mutations in the p150 Glued Subunit Destabilize the CAP-gly Domain

Year: 2010

Type: article

Abstract: 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.

Source: Biochemistry

DOI: 10.1021/bi100235z

Authors: Shubbir Ahmed, Shangjin Sun, Amanda E. Siglin, Tatyana Polenova, John C. Williams

Institutions: City Of Hope National Medical Center, City of Hope, Beckman Research Institute, University of Delaware, Thomas Jefferson University

Language: English

Topic: Genetic Neurodegenerative Diseases

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institute of General Medical Sciences, National Center for Research Resources