4DDP

crystal structure of Beclin 1 evolutionarily conserved domain(ECD)

4DDP の概要

• エントリーDOI: 10.2210/pdb4ddp/pdb
• 分子名称: Beclin-1 (2 entities in total)
• 機能のキーワード: beclin 1, ecd, autophagy, membrane binding, membrane protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Golgi apparatus, trans-Golgi network membrane; Peripheral membrane protein: Q14457
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 24459.81

構造登録者

Huang, W.J.,Choi, W.Y.,Wang, J.W.,Shi, Y.G. (登録日: 2012-01-19, 公開日: 2012-02-22, 最終更新日: 2024-03-20)

主引用文献

Huang, W.,Choi, W.,Hu, W.,Mi, N.,Guo, Q.,Ma, M.,Liu, M.,Tian, Y.,Lu, P.,Wang, F.L.,Deng, H.,Liu, L.,Gao, N.,Yu, L.,Shi, Y.
Crystal structure and biochemical analyses reveal Beclin 1 as a novel membrane binding protein
Cell Res., 2012

PubMed Abstract: The Beclin 1 gene is a haplo-insufficient tumor suppressor and plays an essential role in autophagy. However, the molecular mechanism by which Beclin 1 functions remains largely unknown. Here we report the crystal structure of the evolutionarily conserved domain (ECD) of Beclin 1 at 1.6 Å resolution. Beclin 1 ECD exhibits a previously unreported fold, with three structural repeats arranged symmetrically around a central axis. Beclin 1 ECD defines a novel class of membrane-binding domain, with a strong preference for lipid membrane enriched with cardiolipin. The tip of a surface loop in Beclin 1 ECD, comprising three aromatic amino acids, acts as a hydrophobic finger to associate with lipid membrane, consequently resulting in the deformation of membrane and liposomes. Mutation of these aromatic residues rendered Beclin 1 unable to stably associate with lipid membrane in vitro and unable to fully rescue autophagy in Beclin 1-knockdown cells in vivo. These observations form an important framework for deciphering the biological functions of Beclin 1.

PubMed: 22310240
DOI: 10.1038/cr.2012.24

実験手法

X-RAY DIFFRACTION (1.547 Å)