Curtin Medical School, Curtin Health Innovation Research Institute, GPO Box U1987, Perth, WA 6845, Australia.
Curtin Institute for Computation, Curtin University, GPO Box U1987, Perth, WA 6845, Australia.
Int J Mol Sci. 2023 Mar 26;24(7):6262. doi: 10.3390/ijms24076262.
Pathogenic fungal diseases in crops are mediated by the release of effector proteins that facilitate infection. Characterising the structure of these fungal effectors is vital to understanding their virulence mechanisms and interactions with their hosts, which is crucial in the breeding of plant cultivars for disease resistance. Several effectors have been identified and validated experimentally; however, their lack of sequence conservation often impedes the identification and prediction of their structure using sequence similarity approaches. Structural similarity has, nonetheless, been observed within fungal effector protein families, creating interest in validating the use of computational methods to predict their tertiary structure from their sequence. We used Rosetta ab initio modelling to predict the structures of members of the ToxA-like and MAX effector families for which experimental structures are known to validate this method. An optimised approach was then used to predict the structures of phenotypically validated effectors lacking known structures. Rosetta was found to successfully predict the structure of fungal effectors in the ToxA-like and MAX families, as well as phenotypically validated but structurally unconfirmed effector sequences. Interestingly, potential new effector structural families were identified on the basis of comparisons with structural homologues and the identification of associated protein domains.
作物中的病原真菌病是由释放有助于感染的效应蛋白介导的。对这些真菌效应子的结构进行特征描述对于了解它们的毒力机制和与宿主的相互作用至关重要，这对于培育具有抗病性的植物品种至关重要。已经鉴定和实验验证了几种效应子；然而，由于它们缺乏序列保守性，通常会阻碍使用序列相似性方法来识别和预测其结构。尽管如此，在真菌效应蛋白家族内观察到了结构相似性，这使得人们有兴趣验证使用计算方法根据其序列预测其三级结构的有效性。我们使用 Rosetta 从头建模来预测 ToxA 样和 MAX 效应子家族成员的结构，这些家族的成员具有已知的实验结构来验证这种方法。然后使用优化的方法来预测具有已知结构的表型验证效应子的结构。结果发现 Rosetta 成功地预测了 ToxA 样和 MAX 家族中真菌效应子的结构，以及表型验证但结构未确认的效应子序列的结构。有趣的是，根据与结构同源物的比较以及相关蛋白结构域的鉴定，确定了潜在的新效应子结构家族。
