3QOF

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

3QOF の概要

• エントリーDOI: 10.2210/pdb3qof/pdb
• 関連するPDBエントリー: 3QNU
• 分子名称: Atlastin-1, GUANOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: gtpase, homotypic fusion, fusion of er membranes, gdp, gtp, endoplasmic reticulum, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Endoplasmic reticulum membrane; Multi-pass membrane protein: Q8WXF7
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 212744.46

構造登録者

Liu, X. (登録日: 2011-02-09, 公開日: 2011-03-02, 最終更新日: 2023-11-01)

主引用文献

Bian, X.,Klemm, R.W.,Liu, T.Y.,Zhang, M.,Sun, S.,Sui, X.,Liu, X.,Rapoport, T.A.,Hu, J.
Structures of the atlastin GTPase provide insight into homotypic fusion of endoplasmic reticulum membranes.
Proc.Natl.Acad.Sci.USA, 108:3976-3981, 2011

PubMed Abstract: 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.

PubMed: 21368113
DOI: 10.1073/pnas.1101643108

実験手法

X-RAY DIFFRACTION (2.802 Å)