Namikawa Yuto, Zhu Lingxiao, Lu Peng, Nagata Koji, Suzuki Michio
Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
Liangzhu Laboratory, Zhejiang University, Hangzhou, China.
Protein Sci. 2025 Nov;34(11):e70336. doi: 10.1002/pro.70336.
Pf-SCP is an EF-hand protein identified in Pinctada fucata that is responsible for calcium transport and concentration in the mantle for shell formation. Previous studies have reported the calcium-binding properties of the EF-hand domains and the localization of Pf-SCP. To understand the calcification from Pf-SCP as a source of calcium, the dissociation of calcium from Pf-SCP must be investigated. However, calcium dissociation from EF-hand proteins, particularly in the presence of carbonate ions, remains poorly understood. In this study, we demonstrated that calcium dissociation from Pf-SCP was induced by carbonate ions using the fluorescence spectra of Pf-SCP, and this was followed by the synthesis of calcium carbonate that was characterized using scanning electron microscope-energy dispersive X-ray spectrometry (SEM-EDS). To gain insight into the calcium dissociation of Pf-SCP at the atomic level, we conducted molecular dynamics simulations using a multi-state ion model for calcium ions. The proposed mechanism of calcium dissociation in Pf-SCP is as follows: Water molecules first replace the amino acids in the EF-hand domain to coordinate calcium ions. Next, the carbonate ions bind to the calcium ions, decreasing the binding affinity of the EF-hand domains for the calcium ions. Finally, the calcium ions detach from the EF-hand, forming a complex with water molecules and carbonate ions. These findings provide a detailed understanding of the structural dynamics of calcium dissociation and the biomineralization mechanism in P. fucata, particularly in relation to the mantle calcification process.
Pf-SCP是在合浦珠母贝中鉴定出的一种EF手型蛋白,负责在贝壳形成的外套膜中进行钙的运输和浓缩。先前的研究报道了EF手型结构域的钙结合特性以及Pf-SCP的定位。为了理解作为钙源的Pf-SCP的钙化过程,必须研究Pf-SCP中钙的解离。然而,EF手型蛋白的钙解离,尤其是在碳酸根离子存在的情况下,仍知之甚少。在本研究中,我们利用Pf-SCP的荧光光谱证明碳酸根离子可诱导Pf-SCP中的钙解离,随后合成了碳酸钙,并使用扫描电子显微镜-能量色散X射线光谱法(SEM-EDS)对其进行了表征。为了在原子水平上深入了解Pf-SCP的钙解离,我们使用钙离子的多态离子模型进行了分子动力学模拟。Pf-SCP中钙解离的 proposed 机制如下:水分子首先取代EF手型结构域中的氨基酸以配位钙离子。接下来,碳酸根离子与钙离子结合,降低了EF手型结构域对钙离子的结合亲和力。最后,钙离子从EF手中脱离,与水分子和碳酸根离子形成复合物。这些发现为合浦珠母贝中钙解离的结构动力学和生物矿化机制提供了详细的理解,特别是与外套膜钙化过程相关的机制。