Studies of casein micelle structure: the past and the present

At the heart of the milk system are the colloidal casein-calcium-transport complexes termed the casein micelles. The application of physical chemical techniques such as light, neutron, and X-ray scattering, and Electron Microscopy (EM) has yielded a wealth of experimental detail concerning the structure of the casein micelle. From these experimental data bases have arisen two conflicting models for the internal structure of the casein micelle. One model emphasizes protein submicellar structures as the dominant feature, while the other proposes that inorganic calcium phosphate nanoclusters serve this function. In this study, these models are critically examined in light of the two current primary dogmas of structural biology which are: protein structure gives rise to function and that competent and productive protein-protein interactions (associations) will lead to efficient transit through the mammary secretory apparatus. In this light an overwhelming argument can be made for the formation of proteinaceous complexes (submicelles) as the formative agents in the synthesis of casein micelles in mammary tissue. Whether these submicelles persist in milk has been questioned. Recently we have carried out studies on casein micelles and submicelles using Atomic Force Microscopy (AFM) and high resolution Transmission Electron Microscopy (TEM) to gain insights on the nature of protein-protein interactions in submicelles and micelles from a structural biology perspective. The results provide experimental evidence that protein-protein interactions are important in the formation and stabilization of casein micelles. milk / micelle / casein / structure / protein-protein interaction 摘要 – 酪蛋白胶束结构研究的回顾与展望。酪蛋白胶束是由酪蛋白与钙盐形成胶体, 酪蛋 白胶束是乳系统的核心。采用物理化学方法, 如光、中子、X-射线散射及电子显微镜技术 等方法对酪蛋白胶束结构给予了详细的分析。现有的资料对酪蛋白内部结构的解释已经形 成了两个互相矛盾的模型, 一种是强调酪蛋白结构的亚胶束模型, 而另一种是认为无机磷酸 钙和酪蛋白形成的纳米簇结构。在本研究中基于两种目前公认的结构生物学理论,即蛋白的 结构赋予其功能性和高效的蛋白-蛋白之间相互作用 (凝聚) 导致其通过乳腺分泌器官进行有 效的转移过程, 对这些模型进行了严格的验证。目前更多的理论观点认为在乳腺组织中的酪 蛋白胶束是以蛋白质复合物也就是亚胶束结构存在。但是亚胶束结构观点受到了质疑。近 来我们采用原子力显微镜 (AFM) 和高分辨率透射电镜 (TEM) 从结构生物学性质的角度对 酪蛋白胶束和亚胶束中蛋白质之间的相互作用进行了研究。结果证明了蛋白-蛋白的相互作