3Q5D

crystal structure of human Atlastin-1 (residues 1-447) bound to GDP, crystal form 1

3Q5D の概要

• エントリーDOI: 10.2210/pdb3q5d/pdb
• 関連するPDBエントリー: 3Q5E
• 分子名称: Atlastin-1, GUANOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: g protein, gtpase, gdp/gtp binding, 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: 1
• 化学式量合計: 52254.56

構造登録者

Byrnes, L.J.,Sondermann, H. (登録日: 2010-12-28, 公開日: 2011-01-19, 最終更新日: 2024-11-20)

主引用文献

Byrnes, L.J.,Sondermann, H.
Structural basis for the nucleotide-dependent dimerization of the large G protein atlastin-1/SPG3A.
Proc.Natl.Acad.Sci.USA, 108:2216-2221, 2011

PubMed Abstract: The large GTPase atlastin belongs to the dynamin superfamily that has been widely implicated in facilitating membrane tubulation, fission, and in select cases, fusion. Mutations spread across atlastin isoform 1 (atlastin-1) have been identified in patients suffering from hereditary spastic paraplegia (HSP), a neurodegenerative disorder affecting motor neuron function in the lower extremities. On a molecular level, atlastin-1 associates with high membrane curvature and fusion events at the endoplasmic reticulum and cis-Golgi. Here we report crystal structures of atlastin-1 comprising the G and middle domains in two different conformations. Although the orientation of the middle domain relative to the G domain is different in the two structures, both reveal dimeric assemblies with a common, GDP-bound G domain dimer. In contrast, dimer formation in solution is observed only in the presence of GTP and transition state analogs, similar to other G proteins that are activated by nucleotide-dependent dimerization. Analyses of solution scattering data suggest that upon nucleotide binding, the protein adopts a somewhat extended, dimeric conformation that is reminiscent of one of the two crystal structures. These structural studies suggest a model for nucleotide-dependent regulation of atlastin with implications for membrane fusion. This mechanism is affected in several mutants associated with HSP, providing insights into disease pathogenesis.

PubMed: 21220294
DOI: 10.1073/pnas.1012792108

実験手法

X-RAY DIFFRACTION (2.699 Å)