6B9G

human ATL1 GTPase domain bound to GDP

Summary for 6B9G

• Entry DOI: 10.2210/pdb6b9g/pdb
• Descriptor: Atlastin-1, GUANOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: gtpase, dynamin related protein, gtpase domain, hydrolase
• Biological source: Homo sapiens (Human)
• Cellular location: Endoplasmic reticulum membrane ; Multi-pass membrane protein : Q8WXF7
• Total number of polymer chains: 4
• Total formula weight: 158082.78

Authors

O'Donnell, J.P.,Sondermann, H. (deposition date: 2017-10-10, release date: 2017-12-06, Last modification date: 2023-10-04)

Primary citation

O'Donnell, J.P.,Byrnes, L.J.,Cooley, R.B.,Sondermann, H.
A hereditary spastic paraplegia-associated atlastin variant exhibits defective allosteric coupling in the catalytic core.
J. Biol. Chem., 293:687-700, 2018

PubMed 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 paraplegia mutant, ATL1-F151S, that is impaired in its nucleotide-hydrolysis cycle but can still adopt a high-affinity homodimer when bound to a transition-state analog. Crystal structures of mutant proteins yielded models of the monomeric pre- and post-hydrolysis states of ATL. Together, these findings define a mechanism for allosteric coupling in which Phe is the central residue in a hydrophobic interaction network connecting the active site to an interdomain interface responsible for nucleotide loading.

PubMed: 29180453
DOI: 10.1074/jbc.RA117.000380

Experimental method

X-RAY DIFFRACTION (3 Å)