A hereditary spastic paraplegia-associated atlastin variant exhibits defective allosteric coupling in the catalytic core.

ABSTRACT: The dynamin-related GTPase atlastin (ATL) catalyzes membrane fusion of the endoplasmic reticulum and thus establishes a network of branched membrane tubules. When ATL function is compromised, the morphology of the endoplasmic reticulum deteriorates, and these defects can result in neurological disorders such as hereditary spastic paraplegia and hereditary sensory neuropathy. ATLs harness the energy of GTP hydrolysis to initiate a series of conformational changes that enable homodimerization and subsequent membrane fusion. Disease-associated amino acid substitutions cluster in regions adjacent to ATL's catalytic site, but the consequences for the GTPase's molecular mechanism are often poorly understood. Here, we elucidate structural and functional defects of an atypical hereditary spastic p

SUBMITTER: O'Donnell JP 

PROVIDER: S-EPMC5767872 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature