4DDP

crystal structure of Beclin 1 evolutionarily conserved domain(ECD)

Summary for 4DDP

• Entry DOI: 10.2210/pdb4ddp/pdb
• Descriptor: Beclin-1 (2 entities in total)
• Functional Keywords: beclin 1, ecd, autophagy, membrane binding, membrane protein
• Biological source: Homo sapiens (human)
• Cellular location: Golgi apparatus, trans-Golgi network membrane; Peripheral membrane protein: Q14457
• Total number of polymer chains: 1
• Total formula weight: 24459.81

Authors

Huang, W.J.,Choi, W.Y.,Wang, J.W.,Shi, Y.G. (deposition date: 2012-01-19, release date: 2012-02-22, Last modification date: 2024-03-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.547 Å)