The guanylyl cyclase-activating protein 1, GCAP1, activates or inhibits retinal guanylyl cyclase (retGC) depending on cellular Ca²⁺ concentrations. Several point mutations of GCAP1 have been associated with impaired calcium sensitivity that eventually triggers progressive retinal degeneration. In this work, we demonstrate that the recombinant human protein presents a highly dynamic monomer-dimer equilibrium, whose dissociation constant is influenced by salt concentration and, more importantly, by protein binding to Ca²⁺ or Mg²⁺. Based on small-angle X-ray scattering data, protein-protein docking, and molecular dynamics simulations we propose two novel three-dimensional models of Ca²⁺-bound GCAP1 dimer. The different propensity of human GCAP1 to dimerize suggests structural differences induced by cation binding potentially involved in the regulation of retGC activity.

中文翻译：

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Ca2+ 或 Mg2+ 对鸟苷酸环化酶激活蛋白 1 (GCAP1) 二聚体组装的调节：了解蛋白质活性的提示

鸟苷酸环化酶激活蛋白 1，GCAP1，根据细胞 Ca ²⁺浓度激活或抑制视黄醛鸟苷酸环化酶 (retGC) 。GCAP1 的几个点突变与钙敏感性受损有关，最终引发进行性视网膜变性。在这项工作中，我们证明重组人蛋白质呈现高度动态的单体-二聚体平衡，其解离常数受盐浓度的影响，更重要的是，受蛋白质与 Ca ²⁺或 Mg ^{2+ 的结合影响}。基于小角度 X 射线散射数据、蛋白质-蛋白质对接和分子动力学模拟，我们提出了两种新型 Ca ²⁺三维模型结合的 GCAP1 二聚体。人类 GCAP1 不同的二聚化倾向表明由可能参与 retGC 活性调节的阳离子结合诱导的结构差异。