Mo H, Moore R C, Cohen F E, Westaway D, Prusiner S B, Wright P E, Dyson H J
Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2352-7. doi: 10.1073/pnas.051627998.
The downstream prion-like protein (doppel, or Dpl) is a paralog of the cellular prion protein, PrP(C). The two proteins have approximately 25% sequence identity, but seem to have distinct physiologic roles. Unlike PrP(C), Dpl does not support prion replication; instead, overexpression of Dpl in the brain seems to cause a completely different neurodegenerative disease. We report the solution structure of a fragment of recombinant mouse Dpl (residues 26-157) containing a globular domain with three helices and a small amount of beta-structure. Overall, the topology of Dpl is very similar to that of PrP(C). Significant differences include a marked kink in one of the helices in Dpl, and a different orientation of the two short beta-strands. Although the two proteins most likely arose through duplication of a single ancestral gene, the relationship is now so distant that only the structures retain similarity; the functions have diversified along with the sequence.
下游类朊病毒蛋白（多配体蛋白聚糖，或Dpl）是细胞朊病毒蛋白PrP(C)的旁系同源物。这两种蛋白质的序列同一性约为25%，但似乎具有不同的生理作用。与PrP(C)不同，Dpl不支持朊病毒复制；相反，Dpl在大脑中的过表达似乎会引发一种完全不同的神经退行性疾病。我们报道了重组小鼠Dpl（第26至157位氨基酸残基）片段的溶液结构，该片段包含一个具有三个螺旋和少量β结构的球状结构域。总体而言，Dpl的拓扑结构与PrP(C)非常相似。显著差异包括Dpl中一个螺旋有明显的扭结，以及两条短β链的方向不同。尽管这两种蛋白质很可能是通过单个祖先基因的复制产生的，但现在它们的关系非常疏远，只有结构保留相似性；功能已随序列而多样化。
