Crystal structure and biochemical analyses reveal Beclin 1 as a novel membrane binding protein.
Crystal structure and biochemical analyses reveal Beclin 1 as a novel membrane binding protein.
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晶体结构和生化分析表明 Beclin 1 是一种新型膜结合蛋白
作者：
Beclin 1基因是一种单倍不足的肿瘤抑制基因，在自噬中起着重要作用。然而，Beclin 1发挥作用的分子机制在很大程度上仍然未知。在这里，我们报告的晶体结构的进化保守结构域（ECD）的Beclin 1在1.6 nm分辨率。Beclin 1 ECD具有一个以前未报道的折叠，具有三个围绕中心轴对称排列的结构重复。Beclin 1 ECD定义了一类新的膜结合结构域，具有对富含心磷脂的脂质膜的强烈偏好。Beclin 1ECD的表面环的尖端由三个芳香族氨基酸组成，作为疏水指与脂质膜结合，从而导致膜和脂质体的变形。这些芳香族残基的突变使得Beclin 1在体外不能稳定地与脂质膜结合，并且在体内不能完全拯救Beclin 1敲低细胞中的自噬。这些观察结果构成了破译Beclin 1生物学功能的重要框架。
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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影响因子：
19
作者：
Funderburk SF;Wang QJ;Yue Z
通讯作者：
Yue Z
影响因子：
3.1
作者：
Gias, E.;Nielsen, S. U.;Morgan, L. A. E.;Toms, G. L.
通讯作者：
Toms, G. L.
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
13.3
作者：
Furuya, Norihiko;Yu, Jie;Levine, Beth
通讯作者：
Levine, Beth
影响因子：
3.4
作者：
deKroon, AIPM;Dolis, D;deKruijff, B
通讯作者：
deKruijff, B