膜联蛋白A2四聚体的排列及其对支撑脂质双层膜结构和扩散性能的影响
Arrangement of Annexin A2 tetramer and its impact on the structure and diffusivity of supported lipid bilayers
摘要：
膜联蛋白是以Ca 2+依赖性方式与阴离子磷脂膜结合的蛋白质家族。膜联蛋白A2与S100 A10（p11）蛋白二聚体形成异源四聚体（Anx A2 t）。该四聚体能够桥接磷脂膜，并且已表明其在转移性细胞的Ca 2+依赖性胞吐和细胞-细胞黏附中起作用。在这里，我们采用X-射线反射率测量来解决的构象Anx A2 t后，钙离子依赖性结合到单一支持的脂质双层（SLB）组成的不同混合物的阴离子（POPS）和中性（POPC）磷脂。基于我们的结果，我们提出Anx A2 t以并排构型结合，即，两个AnxA 2单体结合到双层上，p11二聚体位于顶部。此外，我们观察到一个强烈的下降后，结合的Anx A2 t的SLB与不同的POPS含量的脂质流动性。X射线反射率测量表明，结合的Anx A2 t也增加了SLB的密度。有趣的是，在SLB的面向蛋白质的小叶中，脂质密度高于面向基质的小叶。这种不对称致密化的脂质双分子层的Anx A2 t和Ca 2+可能有重要的意义的生化机制的Anx A2 t诱导的内分泌和胞吐。
英文摘要：
Annexins are a family of proteins that bind to anionic phospholipid membranes in a Ca2+-dependent manner. Annexin A2 forms heterotetramers (Anx A2t) with the S100A10 (p11) protein dimer. The tetramer is capable of bridging phospholipid membranes and it has been suggested to play a role in Ca2+-dependent exocytosis and cell-cell adhesion of metastatic cells. Here, we employ x-ray reflectivity measurements to resolve the conformation of Anx A2t upon Ca2+-dependent binding to single supported lipid bilayers (SLBs) composed of different mixtures of anionic (POPS) and neutral (POPC) phospholipids. Based on our results we propose that Anx A2t binds in a side-by-side configuration, i.e., both Anx A2 monomers bind to the bilayer with the p11 dimer positioned on top. Furthermore, we observe a strong decrease of lipid mobility upon binding of Anx A2t to SLBs with varying POPS content. X-ray reflectivity measurements indicate that binding of Anx A2t also increases the density of the SLB. Interestingly, in the protein-facing leaflet of the SLB the lipid density is higher than in the substrate-facing leaflet. This asymmetric densification of the lipid bilayer by Anx A2t and Ca2+ might have important implications for the biochemical mechanism of Anx A2t-induced endo- and exocytosis.
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