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PDBsum entry 4ddp
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Membrane protein
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PDB id
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4ddp
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References listed in PDB file
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Key reference
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Title
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Crystal structure and biochemical analyses reveal beclin 1 as a novel membrane binding protein.
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Authors
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W.Huang,
W.Choi,
W.Hu,
N.Mi,
Q.Guo,
M.Ma,
M.Liu,
Y.Tian,
P.Lu,
F.L.Wang,
H.Deng,
L.Liu,
N.Gao,
L.Yu,
Y.Shi.
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Ref.
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Cell Res, 2012,
22,
473-489.
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PubMed id
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Abstract
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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.
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