School of Pharmacy and Biomedical Sciences, Curtin Health and Innovation Research Institute, Curtin University, Perth WA 6845, Australia.
Curtin Institute for Computation, Curtin University, Perth WA 6845, Australia.
Int J Mol Sci. 2019 Aug 26;20(17):4168. doi: 10.3390/ijms20174168.
Several proteins other than the frizzled receptors (Fzd) and the secreted Frizzled-related proteins (sFRP) contain Fzd-type cysteine-rich domains (CRD). We have termed these domains "putative Fzd-type CRDs", as the relevance of Wnt signalling in the majority of these is unknown; the RORs, an exception to this, are well known for mediating non-canonical Wnt signalling. In this study, we have predicted the likely binding affinity of all Wnts for all putative Fzd-type CRDs. We applied both our previously determined Wnt‒Fzd CRD binding affinity prediction model, as well as a newly devised model wherein the lipid term was forced to contribute favourably to the predicted binding energy. The results obtained from our new model indicate that certain putative Fzd CRDs are much more likely to bind Wnts, in some cases exhibiting selectivity for specific Wnts. The results of this study inform the investigation of Wnt signalling modulation beyond Fzds and sFRPs.
除了卷曲受体（Fzd）和分泌型卷曲相关蛋白（sFRP）之外，还有几种蛋白质含有卷曲受体型富含半胱氨酸结构域（CRD）。我们将这些结构域称为“推定的卷曲受体型 CRD”，因为大多数情况下这些结构域与 Wnt 信号通路的相关性未知；ROR 是一个例外，它以介导非经典 Wnt 信号通路而闻名。在这项研究中，我们预测了所有推定的卷曲受体型 CRD 与所有 Wnt 的可能结合亲和力。我们应用了我们之前确定的 Wnt-Fzd CRD 结合亲和力预测模型，以及一个新设计的模型，其中强制脂质项对预测的结合能产生有利影响。我们新模型的结果表明，某些推定的卷曲受体 CRD 更有可能与 Wnt 结合，在某些情况下表现出对特定 Wnt 的选择性。这项研究的结果为 Fzds 和 sFRPs 之外的 Wnt 信号通路调节提供了信息。
