Isbell Sara L, Haslam Simone B, Zankel Todd C
Raptor Pharmaceutical Inc., 9 Commercial Boulevard, Suite 200, Novato, CA 94949, USA.
Biochem Biophys Res Commun. 2007 Sep 28;361(3):758-62. doi: 10.1016/j.bbrc.2007.07.058. Epub 2007 Jul 26.
The third domain of the low-density lipoprotein receptor-associated protein (RAP d3) binds with high-affinity to pairs of complement-type repeats (CR) within the LDLR family of receptors. Structural analyses have defined the contact surface between RAP d3 and a CR pair from the low-density lipoprotein receptor (LDLR). Much of the sequence of RAP d3 has been proposed to stabilize the receptor-binding region without participating directly in formation of the contact surface. We have developed a truncated version of RAP d3 in which these scaffolding regions are excised and replaced with a single, intramolecular disulfide bond. This substitution allows for deletion of as much as a third of the RAP d3 sequence with substantial retention of receptor-binding ability.
低密度脂蛋白受体相关蛋白（RAP d3）的第三个结构域与低密度脂蛋白受体（LDLR）家族受体中的补体类型重复序列（CR）对具有高亲和力结合。结构分析确定了RAP d3与低密度脂蛋白受体（LDLR）的一对CR之间的接触表面。有人提出，RAP d3的大部分序列可稳定受体结合区域，而不直接参与接触表面的形成。我们开发了一种RAP d3的截短版本，其中切除了这些支架区域，并用单个分子内二硫键取代。这种取代使得RAP d3序列可删除多达三分之一，同时仍能大量保留受体结合能力。
