3qof | pdb_00003qof

Crystal structure of the cytosolic domain of human atlastin-1 in complex with GDP, orthorhombic form

spinqualitylabelsall models 3qof, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3qof is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GDP, MG Related: 3qnu Gene: ATL1, GBP3, SPG3A (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [ATLA1_HUMAN] Hereditary sensory and autonomic neuropathy type 1;Autosomal dominant spastic paraplegia type 3. Spastic paraplegia autosomal dominant 3 (SPG3) [MIM:182600]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. Note=The disease is caused by mutations affecting the gene represented in this entry. Hereditary sensory neuropathy 1D (HSN1D) [MIM:613708]: A disease characterized by adult-onset distal axonal sensory neuropathy leading to mutilating ulcerations as well as hyporeflexia. Some patients may show features suggesting upper neuron involvement. Note=The disease is caused by mutations affecting the gene represented in this entry. Function [ATLA1_HUMAN] GTPase tethering membranes through formation of trans-homooligomer and mediating homotypic fusion of endoplasmic reticulum membranes. Functions in endoplasmic reticulum tubular network biogenesis. May also regulate Golgi biogenesis. May regulate axonal development. Publication Abstract from PubMed The generation of the tubular network of the endoplasmic reticulum (ER) requires homotypic membrane fusion that is mediated by the dynamin-like, membrane-bound GTPase atlastin (ATL). Here, we have determined crystal structures of the cytosolic segment of human ATL1, which give insight into the mechanism of membrane fusion. The structures reveal a GTPase domain and athree-helix bundle, connected by a linker region. One structure corresponds to a prefusion state, in which ATL molecules in apposing membranes interact through their GTPase domains to form a dimer with the nucleotides bound at the interface. The other structure corresponds to a postfusion state generated after GTP hydrolysis and phosphate release. Compared with the prefusion structure, the three-helix bundles of the two ATL molecules undergo a major conformational change relative to the GTPase domains, which could pull the membranes together. The proposed fusion mechanism is supported by biochemical experiments and fusion assays with wild-type and mutant full-length Drosophila ATL. These experiments also show that membrane fusion is facilitated by the C-terminal cytosolic tails following the two transmembrane segments. Finally, our results show that mutations in ATL1 causing hereditary spastic paraplegia compromise homotypic ER fusion. Structures of the atlastin GTPase provide insight into homotypic fusion of endoplasmic reticulum membranes.,Bian X, Klemm RW, Liu TY, Zhang M, Sun S, Sui X, Liu X, Rapoport TA, Hu J Proc Natl Acad Sci U S A. 2011 Mar 8;108(10):3976-81. Epub 2011 Feb 22. PMID:21368113 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Atlastin 3D structures GTP-binding protein 3D structures

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