Energetics and Protomer Communication in the dynamical Structure of S100A13 in Free and Protein-Bound States
Energetics and Protomer Communication in the dynamical Structure of S100A13 in Free and Protein-Bound States
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游离态和蛋白质结合态 S100A13 动态结构中的能量学和原基体通讯
DOI：
10.1080/08927022.2015.1091936
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发表时间：
2015
影响因子：
2.1
通讯作者：
Ueda H
中科院分区：
文献类型：
--
作者：
Omotuyi OI ;Ueda H
S100A13是S100家族的EF-hand含钙结合蛋白，参与一些缺乏信号肽的生长因子和促炎细胞因子的分泌。据报道，S100A13 参与癌症进展和炎症性疾病。在这项研究中，研究了原子分子动力学模拟过程中生成的结构。动态网络分析数据显示，主要由 vdW 相互作用 (~550 kj/mol) 驱动的天然原基体通讯网络在蛋白质结合的 S100A13 同二聚体。所探索的暴露的 S100A13 同二聚体表面周围的体积水密度（加权原子密度）倾向于遵循动态网络主导，因为 S100A13 同二聚体在 C2A-p40Syt1- 和 IL1)-α- 结合状态中出现密集溶剂化，但在 RAGE C2- 和 FGF-1 结合生物系统中则不然。此外，沿 3D 自由能量表面生成的结构的回转半径和均方根偏差（相对于天然结构）变量的投影显示，在从能量最低状态检索到的大多数亚稳态复合物中，反平行 β 折叠接近 Ca2+ 结合环 I/II，强烈表明在蛋白质结合期间形成 β 折叠网络。 S100A13 同二聚体和配体蛋白之间的相互作用可能由 vdW 的强度和静电相互作用决定，可能涉及某些复合物中的大量水去溶剂化。所有这些结果强烈表明，通过设计针对 S100A13/蛋白质相互作用的特定方面的特定化合物，可以实现多蛋白受体复合物的破坏；此类药物在阻断血管生成、逆转细胞增殖和减轻炎症过程方面可能具有临床用途。
S100A13 is S100 family of EF-hand-containing calcium-binding protein involved in the secretion of some growth factors and pro-inflammatory cytokines lacking signal peptides. The involvement of S100A13 in cancer progression and inflammatory diseases has been reported. In this study, structures generated during atomistic molecular dynamics simulation were studied. Dynamical network analysis data revealed that native inter-protomer communication network driven principally by vdW interaction (~550 kj/mol) is altered (Receptor for advanced glycation end products (RAGE) C2- and Fibroblast growth factor (FGF)-1-bound S100A13) or completely abolished (interleukin-1 (IL1)-α- and C2A-p40Syt1-bound S100A13) in protein-bound S100A13 homodimer. Bulk water density (weighted atomic density) around exposed S100A13 homodimer surface explored tends to follow the dynamical network lead as S100A13 homodimer appeared densely solvated in C2A-p40Syt1- and IL1)-α-bound states but not in RAGE C2- and FGF-1-bound biosystems. Furthermore, projection of radius of gyration and root mean square deviation (from native structure) variables of the generated structures along the 3D-free energy surface showed anti-parallel β-sheet proximal to Ca2+-binding loops-I/II in most metastable complexes retrieved from energy minima state with strong indications for β-sheet network formation during protein binding. Interaction between S100A13 homodimer and ligand–proteins may be dictated by the strength of vdW and electrostatic interaction with possible involvement of bulk water desolvation in some complexes. All these results strongly suggest that disruption of multiprotein receptor complex can be achieved by designing specific compounds targeting a specific aspect of S100A13/protein interaction; such drugs may have clinical usefulness in blocking angiogenesis, reversing cell proliferation and attenuating inflammatory processes.