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常染色体隐性小脑症(autosomal recessive primary microcephaly,MCPH)是一种与大脑缩小和智力缺陷有关的神经发育障碍.ASPM (abnormal spindle-like microcephaly-associated)是最常见的MCPH致病基因,但其潜在机制尚不清楚.研究发现,钙调蛋白(calmodulin,CaM)通过与ASPM的IQ区域相互作用而对ASPM的功能有重要调控作用.我们纯化了ASPM IQ区域和CaM的复合物,并通过分子排阻色谱结合多角度静态光散射(SEC-MALS)和圆二光谱(CD)实验发现,ASPM和apo_CaM的结合比例为1∶8.有趣的是,在Ca2+存在时,ASPM的IQ区域与Ca2+ CaM的结合比例变为了1∶7.此外,通过比较不同条件下(Ca2+存在与否)的CD光谱,ASPM-CaM复合物显示出Ca2+依赖性的热稳定性变化.综上所述,该研究揭示了Ca2+诱导的ASPM-CaM相互作用的调节机制.“,”Autosomal recessive primary microcephaly is a neurodevelopmental disorder associated with reduced brain size and intellectual disability.ASPM (abnormal spindle-like microcephaly-associated) is the most common recessive microcephaly gene,but the underlying mechanism is poorly understood.Here,we show that calmodulin function as a vital regulator of ASPM by interacting with its IQ-region.The complex of ASPM IQ-region and apo_calmodulin was purified and biochemically characterized with a 1∶8 stoichiometry by size exclusion chromatography coupled with multi-angle static light scattering (SEC-MALS) and circular dichroism spectroscopy (CD).Interestingly,the binding ratio of ASPM IQ-region with Ca2+_calmodulin changed to 1∶7 in the presence of Ca2+.In addition,by comparing the CD spectra with and without Ca2+,the ASPM-Calmodulin complex showed Ca2+-dependent thermal stability change.Taken together,these results suggested a Ca2+-induced regulation mechanism of ASPM-calmodulin interaction.