5vgr
Human Atlastin-3, GDP-bound
Structural highlights
DiseaseATLA3_HUMAN Hereditary sensory and autonomic neuropathy type 1. The disease is caused by mutations affecting the gene represented in this entry. FunctionATLA3_HUMAN GTPase tethering membranes through formation of trans-homooligomers and mediating homotypic fusion of endoplasmic reticulum membranes. Functions in endoplasmic reticulum tubular network biogenesis.[1] [2] Publication Abstract from PubMedThe endoplasmic reticulum (ER) forms a branched, dynamic membrane tubule network that is vital for cellular function. Branching arises from membrane fusion facilitated by the GTPase atlastin (ATL). Many metazoan genomes encode for three ATL isoforms that appear to fulfill partially redundant function despite differences in their intrinsic GTPase activity and localization within the ER; however, the underlying mechanistic differences between the isoforms are poorly understood. Here, we identify discrete temporal steps in the catalytic cycle for the two most dissimilar isoforms, ATL1 and ATL3, revealing an overall conserved progression of molecular events from nucleotide binding and hydrolysis to ATL dimerization and phosphate release. A crystal structure of ATL3 suggests a mechanism for the displacement of the catalytic Mg2+ ion following guanosine triphosphate (GTP) hydrolysis. Together, the data extend the mechanistic framework for how GTP hydrolysis drives conformational changes in ATL and how the cycle is reset for subsequent rounds of catalysis. Timing and Reset Mechanism of GTP Hydrolysis-Driven Conformational Changes of Atlastin.,O'Donnell JP, Cooley RB, Kelly CM, Miller K, Andersen OS, Rusinova R, Sondermann H Structure. 2017 Jul 5;25(7):997-1010.e4. doi: 10.1016/j.str.2017.05.007. Epub, 2017 Jun 9. PMID:28602821[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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