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PMID: 22310240 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Cell research ·Vol. 22 ·No. 3 ·2012-03-00 ·Pages 473-89

Huang W, Choi W, Hu W, Mi N, Guo Q, Ma M, Liu M, Tian Y, Lu P, Wang FL, Deng H, Liu L, Gao N, Yu L, Shi Y

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.

MeSH Terms
Animals Apoptosis Regulatory Proteins/chemistry,genetics,metabolism Beclin-1 Cells, Cultured HeLa Cells Humans Membrane Proteins/chemistry,genetics,metabolism Models, Molecular Protein Conformation Rats
Chemicals
Apoptosis Regulatory Proteins BECN1 protein, human Beclin-1 Membrane Proteins
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Huang Weijiao
Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing 100084, China.
Choi Wooyoung
Hu Wanqiu
Mi Na
Guo Qiang
Ma Meisheng
Liu Mei
Tian Yuan
Lu Peilong
Wang Feng-Liang
Deng Haiteng
Liu Lei
Gao Ning
Yu Li
Shi Yigong
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Article Info
Journal
Cell research
Abbr.
Cell Res
ISSN
1748-7838
DOI
10.1038/cr.2012.24
Published
2012-03-00
Epub
2012-00-07
Pages
473-89
Language
English
Region
England
NLM ID
9425763
PMCID
PMC3292424
Subset
IM
Databases
PDB
4DDP
External Links
PubMed source DOI: 10.1038/cr.2012.24 PMC Full Text View journal details
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