ABCA1 is an extracellular phospholipid translocase.
ABCA1 is an extracellular phospholipid translocase.
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ABCA1 是一种细胞外磷脂转位酶。
DOI：
10.1038/s41467-022-32437-3
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发表时间：
2022-08-16
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
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作者：
高密度脂蛋白(HDL)的产生需要三磷酸腺苷结合盒转运体A1(ABCA1)将磷脂(PL)从质膜驱动到细胞外载脂蛋白A-I。在这里，我们使用模拟来证明质膜内的ABCA1结构域从膜的外层小叶中去除PL。在我们的模拟中，当脂质扩散到ABCA1的S外开空腔内部后，由网关提取的PL穿过一个环状结构域，即环孔，它在转运蛋白的胞外域中形成了一个细长的疏水隧道的底部。通道和环中的工程突变强烈地抑制ABCA1的脂类输出，而不影响细胞表面的表达水平。我们的发现是，ABCA1从质膜的外表面提取脂类，并迫使其通过其网关和环路进入一个细长的疏水隧道，这与交替进入模型形成了鲜明对比，该模型认为ABCA1将PL底物从膜的内叶转移到膜的外叶。与我们的模型一致，ABCA1缺乏在ABC转运蛋白家族的Floppase成员中发现的跨膜区的带电氨基酸残基。三磷酸腺苷结合盒转运体A1(ABCA1)驱动磷脂(PL)从细胞膜进入细胞外的载脂蛋白A-I，以产生高密度脂蛋白(HDL)。在这里，作者使用模拟来评估ABCA1功能的机制，并表明ABCA1从质膜的外表面提取脂类。
Production of high density lipoprotein (HDL) requires ATP-binding cassette transporter A1 (ABCA1) to drive phospholipid (PL) from the plasma membrane into extracellular apolipoprotein A-I. Here, we use simulations to show that domains of ABCA1 within the plasma membrane remove PL from the membrane’s outer leaflet. In our simulations, after the lipid diffuses into the interior of ABCA1’s outward-open cavity, PL extracted by the gateway passes through a ring-shaped domain, the annulus orifice, which forms the base of an elongated hydrophobic tunnel in the transporter’s extracellular domain. Engineered mutations in the gateway and annulus strongly inhibit lipid export by ABCA1 without affecting cell-surface expression levels. Our finding that ABCA1 extracts lipid from the outer face of the plasma membrane and forces it through its gateway and annulus into an elongated hydrophobic tunnel contrasts with the alternating access model, which proposes that ABCA1 flops PL substrate from the inner leaflet to the outer leaflet of the membrane. Consistent with our model, ABCA1 lacks the charged amino acid residues in the transmembrane domain found in the floppase members of the ABC transporter family. ATP-binding cassette transporter A1 (ABCA1) drives phospholipid (PL) from the plasma membrane into extracellular apolipoprotein A-I, for the production of high density lipoprotein (HDL). Here, the authors use simulations to assess the mechanism of ABCA1 function and show that ABCA1 extracts lipid from the outer face of the plasma membrane.
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影响因子：
6.5
作者：
Duong, PT;Collins, HL;Phillips, MC
通讯作者：
Phillips, MC
影响因子：
14.9
作者：
NCBI Resource Coordinators
通讯作者：
NCBI Resource Coordinators
影响因子：
16.6
作者：
Faustino, Ignacio;Abdizadeh, Haleh;Marrink, Siewert J.
通讯作者：
Marrink, Siewert J.
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
影响因子：
7.7
作者：
Liu F;Lee J;Chen J
通讯作者：
Chen J