X-ray structure of full-length annexin 1 and implications for membrane aggregation
X-ray structure of full-length annexin 1 and implications for membrane aggregation
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DOI：
10.1006/jmbi.2000.4423
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发表时间：
2001-02-23
影响因子：
5.6
通讯作者：
Luecke, H
中科院分区：
文献类型：
--
作者：
Rosengarth, A;Gerke, V;Luecke, H
膜联蛋白是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末端或核心域和一个N末端结构域组成，前者提供钙依赖的磷脂结合，后者在序列和长度上可变，并负责每个膜联蛋白的特定性质。不同膜联蛋白核心区的晶体结构具有高度的相似性。从这些和其他研究中可以明显看出，核心区含有与磷脂头基相互作用的钙结合部位。然而，目前还没有报道具有完整N-末端结构域的膜联蛋白的结构。我们现在已经解决了这种全长膜联蛋白--膜联蛋白1的晶体结构。膜联蛋白1活跃在膜聚集中，其精细的1.8埃结构显示出一个α-螺旋的N-末端结构域通过柔性连接子连接到核心域。令人惊讶的是，41个残基的N-末端结构域中的两个a-螺旋与核心区相互作用密切，N-末端结构域的两亲性螺旋2-12取代了核心重复序列III的螺旋D。反过来，螺旋D被展开成现在部分覆盖N端螺旋的襟翼。将讨论膜聚集的含义，并提出基于结构的聚集模型。(C)2001年学术出版社。
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 Angstrom structure shows an alpha -helical N-terminal domain connected to the core domain by a flexible Linker. It is surprising that the two a-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. (C) 2001 Academic Press.