AN ENERGY-MINIMIZED CASEIN SUBMICELLE WORKING MODEL

To develop a molecular basis for structure-function relationships of t he complex milk protein system, an energy-minimized, three-dimensional model of a casein submicelle was constructed consisting of kappa-case in, four alpha(s1)-casein, and four beta-casein molecules. The models for the individual caseins were from previously reported energy-minimi zed, three-dimensional structures. Docking of one kappa-casein and fou r alpha(s1)-casein molecules produced a framework structure through th e interaction of two hydrophobic antiparallel sheets of kappa-casein w ith two small hydrophobic antiparallel sheets (residue 163-174) of two preformed alpha(s1)-casein dimers. The resulting structure is approxi mately spherically symmetric, with a loose packing density; its extern al portion is composed of the hydrophilic domains of the four alpha(s1 )-caseins, while the central portion contains two hydrophbic cavities on either side of the kappa-casein central structure. Symmetric and as ymmetric preformed dimers of beta-casein formed from the interactions of C-terminal beta-spiral regions as a hinge point could easily be doc ked into each of the two central cavities of the alpha-kappa framework . This yielded two plausible energy-minimized, three-dimensional struc tures for submicellar casein, one with two symmetric beta-casein dimer s and one with two asymmetric dimers. These refined submicellar struct ures are in good agreement with biochemical, chemical, and solution st ructural information available for submicellar casein.