Rosengarth A, Gerke V, Luecke H
Department of Molecular Biology and Biochemistry and UCI Program in Macromolecular Structure, University of California, 3205 Biological Sciences II, Irvine, CA, 92697-3900, USA.
J Mol Biol. 2001 Feb 23;306(3):489-98. doi: 10.1006/jmbi.2000.4423.
Annexins comprise a multigene family of Ca2+ and phospholipid- binding proteins. They consist of a conserved C-terminal or core domain that confers Ca2+-dependent phospholipid binding and an N-terminal domain that is variable in sequence and length and responsible for the specific properties of each annexin. Crystal structures of various annexin core domains have revealed a high degree of similarity. From these and other studies it is evident that the core domain harbors the calcium-binding sites that interact with the phospholipid headgroups. However, no structure has been reported of an annexin with a complete N-terminal domain. We have now solved the crystal structure of such a full-length annexin, annexin 1. Annexin 1 is active in membrane aggregation and its refined 1.8 A structure shows an alpha-helical N-terminal domain connected to the core domain by a flexible linker. It is surprising that the two alpha-helices present in the N-terminal domain of 41 residues interact intimately with the core domain, with the amphipathic helix 2-12 of the N-terminal domain replacing helix D of repeat III of the core. In turn, helix D is unwound into a flap now partially covering the N-terminal helix. Implications for membrane aggregation will be discussed and a model of aggregation based on the structure will be presented.
膜联蛋白构成了一个由钙离子和磷脂结合蛋白组成的多基因家族。它们由一个保守的C端或核心结构域和一个N端结构域组成，前者赋予钙离子依赖性磷脂结合能力，后者在序列和长度上具有可变特性，并决定了每种膜联蛋白的特定属性。各种膜联蛋白核心结构域的晶体结构显示出高度的相似性。从这些研究以及其他研究中可以明显看出，核心结构域包含与磷脂头部基团相互作用的钙结合位点。然而，尚未有关于具有完整N端结构域的膜联蛋白的结构报道。我们现在已经解析了这样一种全长膜联蛋白——膜联蛋白1的晶体结构。膜联蛋白1在膜聚集过程中具有活性，其精修后的1.8埃结构显示，一个α螺旋N端结构域通过一个柔性连接子与核心结构域相连。令人惊讶的是，由41个残基组成的N端结构域中的两个α螺旋与核心结构域紧密相互作用，N端结构域的两亲性螺旋2-12取代了核心结构域重复III的螺旋D。相应地，螺旋D展开形成一个侧翼，现在部分覆盖了N端螺旋。我们将讨论其对膜聚集的影响，并基于该结构提出一个聚集模型。
