Structural basis of the Ca2+-dependent association between S100C (S100A11) and its target, the N-terminal part of annexin I
Structural basis of the Ca2+-dependent association between S100C (S100A11) and its target, the N-terminal part of annexin I
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DOI：
10.1016/s0969-2126(00)00093-9
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发表时间：
2000-02-15
期刊：
影响因子：
5.7
通讯作者：
Lewit-Bentley, A
中科院分区：
文献类型：
--
作者：
Réty, S;Osterloh, D;Lewit-Bentley, A
背景资料：S100 C（S100 A11）是S100钙结合蛋白家族的成员，其功能尚不完全清楚，但可能包括细胞骨架组装和动力学。S100蛋白由两个EF-手形钙结合基序组成，通过一个灵活的环连接。与该家族的其他几个成员一样，S100 C形成同源二聚体。一些S100蛋白形成复合物与膜联蛋白，另一个家庭的钙结合蛋白，也结合到磷脂，结构研究已进行了解这些interactions.Results的基础：我们已经解决了一个复杂的钙加载S100 C与合成肽，对应于第一个14个残基的膜联蛋白I N末端在2.3埃分辨率的晶体结构。我们发现每个S100 C单体一个肽的化学计量，整个复合物结构由每个S100 C二聚体两个肽组成，然而，每个肽与S100 C二聚体的两个单体相互作用，二聚体的两个S100 C分子通过二硫桥连接。该结构令人惊讶地接近先前解决的pII-膜联蛋白II N-末端肽复合物的结构。我们已经进行了竞争实验，试图了解的特异性：S100-膜联蛋白interaction.Conclusions：通过解决第二膜联蛋白N末端-S100蛋白复合物的结构，我们证实了一种新的模式的相互作用的S100蛋白与它们的目标肽，有一个一对一的化学计量，其中，S100蛋白的二聚体结构，然而，复合物的形成是必不可少的。我们的结构可以提供一个模型的Ca 2+调节膜联蛋白I-S100 C异源四聚体，可能参与交联膜表面：或组织膜在某些融合事件。
Background: S100C (S100A11) is a member of the S100 calcium-binding protein family, the function of which is not yet entirely clear, but:may,include cytoskeleton assembly and dynamics. S100 proteins consist of two EF-hand calcium-binding motifs, connected by a flexible loop. Like several other members of the family, S100C forms a homodimer. A number of S100 proteins form complexes with annexins, another family of calcium-binding proteins that also bind to phospholipids, Structural studies have been undertaken to understand the basis of these interactions.Results: We have solved the crystal structure of a complex of calcium-loaded S100C with a synthetic peptide that corresponds to the first 14 residues-of the annexin I N terminus at 2.3 Angstrom resolution. We find a stoichiometry of one peptide per S100C monomer, the entire complex structure consisting of two peptides per S100C dimer, Each peptide, however, interacts with both monomers of the S100C dimer, The two S100C molecules of the dimer are linked,by a disulphide bridge. The structure is surprisingly close to that of the pll-annexin II N-terminal peptide complex solved previously. We have performed competition experiments to try to understand the specificity:of the S100-annexin interaction.Conclusions: By solving the structure of a second annexin N terminus-S100 protein complex, we confirmed a novel mode of interaction of S100 proteins with their target peptides; there is a one-to-one stoichiometry, where,the dimeric structure of the S100 protein is, nevertheless, essential for complex formation. Our structure can provide a model for a Ca2+-regulated annexin I-S100C heterotetramer, possibly involved in crosslinking membrane surfaces:or organising membranes during certain fusion events.