A calcium-driven conformational switch of the n-terminal and core domains of annexin A1
A calcium-driven conformational switch of the n-terminal and core domains of annexin A1
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DOI：
10.1016/s0022-2836(03)00027-5
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发表时间：
2003-03-07
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;Luecke, H
1993年，Huber和他的同事发表了人类膜联蛋白A1的N末端截短版本的结构，缺少前32个氨基酸残基(PDB代码：1AIN)。2001年，我们报道了猪Annexin A1的全长结构，包括N-末端结构域(PDB代码：1HM6)。后一种结构并没有反映典型的膜联蛋白核心折叠，而是N末端结构域和核心结构域之间令人惊讶的相互作用。比较这两种结构表明，在全长结构中，N-末端结构域的前12个残基插入到蛋白质的核心，从而取代和解开参与钙结合的一个a-螺旋(重复3中的螺旋D)。我们假设，在没有钙离子的情况下，这种结构代表了蛋白质的非活性形式。此外，我们提出，当钙结合时，N-末端结构域将从核心结构域中排出，核心D-螺旋将以合适的构象进行改造，以实现钙的配位。在此，我们报道了全长猪膜联蛋白A1在钙存在下的X射线结构。这种新的结构显示了一个典型的膜联蛋白核心结构，正如我们假设的那样，D-螺旋回到原位进行钙配位，而现在暴露的N-末端结构域的部分是无序的。我们可以在这个结构中定位到8个钙离子，其中两个是八配位的，两个在N末端截短的膜联蛋白A1的结构中没有观察到。这种钙诱导的构象转换对膜联蛋白A1的膜聚集特性的可能影响将被讨论。(C)2003爱思唯尔科学有限公司。保留所有权利。
In 1993, Huber and co-workers published the structure of an N-terminally truncated version of human annexin A1 lacking the first 32 amino acid residues (PDB code: 1AIN). In 2001, we reported the structure of full-length porcine annexin A1 including the N-terminal domain in the absence of calcium ions (PDB code: 1HM6). The latter structure did not reflect a typical annexin core fold, but rather a surprising interaction of the N-terminal domain and the core domain. Comparing these two structures revealed that in the full-length structure the first 12 residues of the N-terminal domain insert into the core of the protein, thereby replacing and unwinding one of the a-helices (helix D in repeat 3) that is involved in calcium binding. We hypothesized that this Structure in the absence of calcium ions represents the inactive form of the protein. Furthermore, we proposed that upon calcium binding, the N-terminal domain would be expelled from the core domain and that the core D-helix would reform in the proper conformation for calcium coordination. Herein, we report the X-ray structure of full-length porcine annexin A1 in the presence of calcium. This new structure shows a typical annexin core structure as we hypothesized, with the D-helix back in place for calcium coordination while parts of the now exposed N-terminal domain are disordered. We could locate eight calcium ions in this structure, two of which are octa-coordinated and two of which were not observed in the structure of the N-terminally truncated annexin A1. Possible implications of this calcium-induced conformational switch for the membrane aggregation properties of annexin A1 will be discussed. (C) 2003 Elsevier Science Ltd. All rights reserved.