Garbuglia M, Verzini M, Donato R
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
Cell Calcium. 1998 Sep;24(3):177-91. doi: 10.1016/s0143-4160(98)90127-0.
Annexin VI, a member of a family of Ca(2+)-dependent phospholipid- and membrane-binding proteins, interacts with the Ca(2+)-regulated EF-hand proteins, S100A1 and S100B, and blocks the ability of these two proteins to inhibit the assembly of desmin and glial fibrillary acidic protein (GFAP) into intermediate filaments in a Ca(2+)- and dose-dependent manner. S100A1 and S100B each possess one annexin VI binding site, characterized by an affinity for annexin VI in the submicromolar range. Binding of annexin VI to either S100 protein occurs at a site that appears to differ in some parts from that recognizing desmin and GFAP. As S100A1 and S100B exist in solution as homodimers in which the two monomers are related by a 2-fold symmetry axis, each of the above S100 homodimers likely crosslinks two annexin VI molecules, a situation that appears typical of all the annexin-S100 protein complexes described thus far. However, whereas in the cases of other annexin-S100 complexes the C-terminal extension of the S100 molecule appears indispensable for annexin binding, the annexin VI binding site cannot be restricted to the S100A1 and S100B C-terminal extension. We speculate that the annexin VI site on S100A1/B may only partially overlap to the desmin/GFAP site. In contrast, no effects of annexin V on the ability of S100A1 or S100B to affect the desmin and GFAP assemblies could be documented, although binding of annexin V to S100A1 and S100B could be detected at relatively high Ca2+ concentrations. The present data suggest that annexin VI might regulate S100A1 and S100B activities and vice versa.
膜联蛋白VI是一种依赖钙离子的磷脂和膜结合蛋白家族的成员，它与钙离子调节的EF手蛋白S100A1和S100B相互作用，并以钙离子和剂量依赖的方式阻断这两种蛋白抑制结蛋白和胶质纤维酸性蛋白（GFAP）组装成中间丝的能力。S100A1和S100B各自拥有一个膜联蛋白VI结合位点，其特征是对亚微摩尔范围内的膜联蛋白VI具有亲和力。膜联蛋白VI与任一S100蛋白的结合发生在一个位点，该位点在某些部分似乎与识别结蛋白和GFAP的位点不同。由于S100A1和S100B在溶液中以同二聚体形式存在，其中两个单体通过二重对称轴相关联，上述每个S100同二聚体可能交联两个膜联蛋白VI分子，这种情况似乎是迄今为止描述的所有膜联蛋白 - S100蛋白复合物的典型情况。然而，在其他膜联蛋白 - S100复合物的情况下，S100分子的C末端延伸对于膜联蛋白结合似乎是必不可少的，但膜联蛋白VI结合位点不能局限于S100A1和S100B的C末端延伸。我们推测S100A1 / B上的膜联蛋白VI位点可能仅与结蛋白/ GFAP位点部分重叠。相比之下，虽然在相对高的钙离子浓度下可以检测到膜联蛋白V与S100A1和S100B的结合，但未发现膜联蛋白V对S100A1或S100B影响结蛋白和GFAP组装能力的作用。目前的数据表明，膜联蛋白VI可能调节S100A1和S100B的活性，反之亦然。
