Human ATG3 binding to lipid bilayers: role of lipid geometry, and electric charge.
Human ATG3 binding to lipid bilayers: role of lipid geometry, and electric charge.
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DOI：
10.1038/s41598-017-15057-6
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发表时间：
2017-11-15
影响因子：
4.6
通讯作者：
Alonso A
中科院分区：
文献类型：
--
作者：
Hervás JH;Landajuela A;Antón Z;Shnyrova AV;Goñi FM;Alonso A
特定的蛋白质-脂质相互作用导致自噬体（AP）形成过程中Autophagosome相关（ATG）蛋白逐渐募集到新生膜。ATG 3是LC 3向隔离膜移动的关键蛋白，已提出促进高度弯曲膜中的LC 3/GABARAP脂化。在这项工作中，我们已经进行了一个生物物理研究的人ATG 3与膜含有磷脂酰乙醇胺，磷脂酰胆碱和阴离子磷脂的相互作用。我们已经发现，ATG 3与带负电荷的磷脂囊泡或纳米管的相互作用比与电中性模型膜更强烈，锥形阴离子磷脂（心磷脂和磷脂酸）在促进结合方面特别活跃。此外，膜曲率的增加促进了ATG 3向膜的募集，尽管阴离子脂质分子的加入使得曲率因子相对不那么重要。ATG 3的预测N-末端两亲性α-螺旋将负责膜曲率检测，阳性残基Lys 9和11在识别磷脂阴性部分中是必需的。我们还观察到由ATG 3在体外诱导的膜聚集，这可能表明该蛋白在AP生物发生中具有更复杂的功能。此外，体外GABARAP脂化测定表明，ATG 3-膜相互作用可以促进ATG 8同系物的脂化。
Specific protein-lipid interactions lead to a gradual recruitment of AuTophaGy-related (ATG) proteins to the nascent membrane during autophagosome (AP) formation. ATG3, a key protein in the movement of LC3 towards the isolation membrane, has been proposed to facilitate LC3/GABARAP lipidation in highly curved membranes. In this work we have performed a biophysical study of human ATG3 interaction with membranes containing phosphatidylethanolamine, phosphatidylcholine and anionic phospholipids. We have found that ATG3 interacts more strongly with negatively-charged phospholipid vesicles or nanotubes than with electrically neutral model membranes, cone-shaped anionic phospholipids (cardiolipin and phosphatidic acid) being particularly active in promoting binding. Moreover, an increase in membrane curvature facilitates ATG3 recruitment to membranes although addition of anionic lipid molecules makes the curvature factor relatively less important. The predicted N-terminus amphipathic α-helix of ATG3 would be responsible for membrane curvature detection, the positive residues Lys 9 and 11 being essential in the recognition of phospholipid negative moieties. We have also observed membrane aggregation induced by ATG3 in vitro, which could point to a more complex function of this protein in AP biogenesis. Moreover, in vitro GABARAP lipidation assays suggest that ATG3-membrane interaction could facilitate the lipidation of ATG8 homologues.
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影响因子：
11.1
作者：
He C;Klionsky DJ
通讯作者：
Klionsky DJ
影响因子：
16.8
作者：
Kaiser, Stephen E.;Mao, Kai;Taherbhoy, Asad M.;Yu, Shanshan;Olszewski, Jennifer L.;Duda, David M.;Kurinov, Igor;Deng, Alan;Fenn, Timothy D.;Klionsky, Daniel J.;Schulman, Brenda A.
通讯作者：
Schulman, Brenda A.
DOI：
10.1073/pnas.1016472108
发表时间：
2011-05-10
影响因子：
11.1
作者：
Fan, Weiliang;Nassiri, Ashley;Zhong, Qing
通讯作者：
Zhong, Qing
影响因子：
3.4
作者：
Fidorra, M.;Duelund, L.;Bagatolli, L. A.
通讯作者：
Bagatolli, L. A.
影响因子：
3.4
作者：
Ibarguren, Maitane;Bomans, Paul H. H.;Goni, Felix M.
通讯作者：
Goni, Felix M.