Self-assembling peptides form nanodiscs that stabilize membrane proteins
Self-assembling peptides form nanodiscs that stabilize membrane proteins
复制标题
DOI：
10.1039/c3sm51727f
复制
发表时间：
2014-01-01
期刊：
影响因子：
3.4
通讯作者：
Arleth, Lise
中科院分区：
文献类型：
--
作者：
Midtgaard, Soren Roi;Pedersen, Martin Cramer;Arleth, Lise
非常需要处理膜结合蛋白，例如G蛋白偶联受体（GPCR）的新方法。最近，基于载脂蛋白A1（ApoA1）的脂蛋白颗粒已经成为研究膜蛋白的新平台，并且已经显示它们可以与磷脂结合自组装以形成可以稳定膜蛋白的盘状颗粒。在本研究中，我们研究了ApoA1模拟肽与磷脂复合时的溶液结构。这是通过使用小角X射线散射（SAXS）和小角中子散射（SANS）的强大组合，并由粗粒度分子动力学模拟支持来实现的。以前所未有的细节确定了盘的详细结构，并且发现它们采用与基于ApoA1的纳米盘非常相似的盘状结构。我们还表明，像ApoA1和衍生的纳米盘，这些肽盘可以容纳和稳定的膜蛋白。最后，我们利用它们的动态特性，并表明，18 A光盘可用于转移膜蛋白和相关的磷脂直接和温和地进入磷脂纳米盘。
New methods to handle membrane bound proteins, e.g. G-protein coupled receptors (GPCRs), are highly desirable. Recently, apoliprotein A1 (ApoA1) based lipoprotein particles have emerged as a new platform for studying membrane proteins, and it has been shown that they can self-assemble in combination with phospholipids to form discoidal shaped particles that can stabilize membrane proteins. In the present study, we have investigated an ApoA1 mimetic peptide with respect to its solution structure when in complex with phospholipids. This was achieved using a powerful combination of small-angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS) supported by coarse-grained molecular dynamics simulations. The detailed structure of the discs was determined in unprecedented detail and it was found that they adopt a discoidal structure very similar to the ApoA1 based nanodiscs. We furthermore show that, like the ApoA1 and derived nanodiscs, these peptide discs can accommodate and stabilize a membrane protein. Finally, we exploit their dynamic properties and show that the 18A discs may be used for transferring membrane proteins and associated phospholipids directly and gently into phospholipid nanodiscs.