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Crystal structure and biochemical analyses reveal Beclin 1 as a novel membrane binding protein.


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.

SUBMITTER: Huang W 

PROVIDER: S-EPMC3292424 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Crystal structure and biochemical analyses reveal Beclin 1 as a novel membrane binding protein.

Huang Weijiao W   Choi Wooyoung W   Hu Wanqiu W   Mi Na N   Guo Qiang Q   Ma Meisheng M   Liu Mei M   Tian Yuan Y   Lu Peilong P   Wang Feng-Liang FL   Deng Haiteng H   Liu Lei L   Gao Ning N   Yu Li L   Shi Yigong Y  

Cell research 20120207 3


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  ...[more]

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