Solution structure of the integral human membrane protein VDAC-1 in detergent micelles
Solution structure of the integral human membrane protein VDAC-1 in detergent micelles
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DOI：
10.1126/science.1161302
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发表时间：
2008-08-29
期刊：
影响因子：
56.9
通讯作者：
Wagner, Gerhard
中科院分区：
文献类型：
--
作者：
Hiller, Sebastian;Garces, Robert G.;Wagner, Gerhard
依赖性阴离子通道（VDAC）介导了小分子和离子在真核外膜上的运输。 VDAC还与BCl-2家族的抗凋亡蛋白相互作用，这种相互作用抑制了线粒体中凋亡蛋白的释放。我们提出重组人VDAC-1在洗涤剂胶束中重组的核磁共振（NMR）溶液结构。它形成了一个19束的β枪管，其第一链和最后一条平行。枪管的疏水外周的外围被皮带状的洗涤剂分子覆盖。在存在胆固醇的情况下，重组VDAC-1可以在类似于天然蛋白的磷脂双层中形成电压通道。 NMR测量结果揭示了Bcl-2蛋白BCl-X（L）的VDAC-1的结合位点，用于降低β-尼古丁酰胺腺嘌呤二核苷酸和胆固醇的结合位点。 Bcl-X（L）在17和18的股线侧面与VDAC枪管相互作用。
The voltage- dependent anion channel ( VDAC) mediates trafficking of small molecules and ions across the eukaryotic outer mitochondrial membrane. VDAC also interacts with antiapoptotic proteins from the Bcl- 2 family, and this interaction inhibits release of apoptogenic proteins from the mitochondrion. We present the nuclear magnetic resonance ( NMR) solution structure of recombinant human VDAC- 1 reconstituted in detergent micelles. It forms a 19- stranded beta barrel with the first and last strand parallel. The hydrophobic outside perimeter of the barrel is covered by detergent molecules in a beltlike fashion. In the presence of cholesterol, recombinant VDAC- 1 can form voltage- gated channels in phospholipid bilayers similar to those of the native protein. NMR measurements revealed the binding sites of VDAC- 1 for the Bcl- 2 protein Bcl-x(L), for reduced beta-nicotinamide adenine dinucleotide, and for cholesterol. Bcl-x(L) interacts with the VDAC barrel laterally at strands 17 and 18.