Gerke Volker, Moss Stephen E
Institute for Medical Biochemistry, Center for Molecular Biology of Inflammation, University of Münster, Münster, Germany.
Physiol Rev. 2002 Apr;82(2):331-71. doi: 10.1152/physrev.00030.2001.
Annexins are Ca2+ and phospholipid binding proteins forming an evolutionary conserved multigene family with members of the family being expressed throughout animal and plant kingdoms. Structurally, annexins are characterized by a highly alpha-helical and tightly packed protein core domain considered to represent a Ca2+-regulated membrane binding module. Many of the annexin cores have been crystallized, and their molecular structures reveal interesting features that include the architecture of the annexin-type Ca2+ binding sites and a central hydrophilic pore proposed to function as a Ca2+ channel. In addition to the conserved core, all annexins contain a second principal domain. This domain, which NH2-terminally precedes the core, is unique for a given member of the family and most likely specifies individual annexin properties in vivo. Cellular and animal knock-out models as well as dominant-negative mutants have recently been established for a number of annexins, and the effects of such manipulations are strikingly different for different members of the family. At least for some annexins, it appears that they participate in the regulation of membrane organization and membrane traffic and the regulation of ion (Ca2+) currents across membranes or Ca2+ concentrations within cells. Although annexins lack signal sequences for secretion, some members of the family have also been identified extracellularly where they can act as receptors for serum proteases on the endothelium as well as inhibitors of neutrophil migration and blood coagulation. Finally, deregulations in annexin expression and activity have been correlated with human diseases, e.g., in acute promyelocytic leukemia and the antiphospholipid antibody syndrome, and the term annexinopathies has been coined.
膜联蛋白是一类能结合钙离子和磷脂的蛋白质，它们构成了一个进化上保守的多基因家族，该家族成员在动物界和植物界均有表达。在结构上，膜联蛋白的特征是具有高度α螺旋且紧密堆积的蛋白质核心结构域，该结构域被认为代表一个受钙离子调节的膜结合模块。许多膜联蛋白的核心结构已被结晶，其分子结构揭示了一些有趣的特征，包括膜联蛋白型钙离子结合位点的结构以及一个被认为作为钙离子通道发挥作用的中央亲水孔。除了保守的核心结构域外，所有膜联蛋白都含有第二个主要结构域。这个结构域在氨基端位于核心结构域之前，对于该家族的特定成员而言是独特的，并且很可能在体内决定了各个膜联蛋白的特性。最近已经为多种膜联蛋白建立了细胞和动物基因敲除模型以及显性负性突变体，而这些操作对该家族不同成员产生的影响显著不同。至少对于某些膜联蛋白而言，它们似乎参与了膜组织和膜运输的调节，以及跨膜离子（钙离子）电流或细胞内钙离子浓度的调节。尽管膜联蛋白缺乏分泌信号序列，但该家族的一些成员也已在细胞外被鉴定出来，在那里它们可以作为内皮细胞上血清蛋白酶的受体，以及中性粒细胞迁移和血液凝固的抑制剂。最后，膜联蛋白表达和活性失调已与人类疾病相关，例如在急性早幼粒细胞白血病和抗磷脂抗体综合征中，并且“膜联蛋白病”这一术语也已被创造出来。
